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Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=NC=C1Br)Br;amine:CN1CCNCC1, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+], and Products are 0:CN1CCN(CC1)C2=CC(=CN=C2)Br, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Trial # 3: 3,5-dibromopyridine (1000 mg, 4.22 mmol), 1-methylpiperazine (423 mg, 4.22 mmol), Pd2(dba)3 (387 mg, 0.42 mmol), XANTPHOS (366 mg, 0.63 mmol), SODIUM TERT-BUTOXIDE (609 mg, 6.33 mmol), PhCH3 (10 mL) as added to a 10 mL microwave vial. This was degassed and refilled with N2 and then heated at 140 °C in microwave for 1h. LCMS showed reaction done with the peak at Rf0.52 showed a fragment mass of 256. Evaporated solvent. Residue purified by (CH3CN/H2O 0-30%+TFA buffer )to get the desired product 1-(5-bromopyridin-3-yl)-4-methylpiperazine (107 mg, 9.90 %). Trial # 1 3,5-dibromopyridine (1000 mg, 4.22 mmol), 1-methylpiperazine (423 mg, 4.22 mmol), Pd2(dba)3 (387 mg, 0.42 mmol), XANTPHOS (366 mg, 0.63 mmol), [Reactants], PhCH3 (5 mL) as added to a 10 mL microwave vial. This was degassed and refilled with N2 and then heated at 140 °C in microwave for 1h. LCMS showed reaction done with no desired peak formed. Trial # 2: 3,5-dibromopyridine (400 mg, 1.69 mmol), 1-methylpiperazine (169 mg, 1.69 mmol), Pd2(dba)3 (155 mg, 0.17 mmol), XANTPHOS (117 mg, 0.20 mmol), SODIUM TERT-BUTOXIDE (243 mg, 2.53 mmol), PhCH3 (5 mL) as added to a 10 mL microwave vial. This was degassed and refilled with N2 and then heated at 140 °C in microwave for 1h. LCMS showed reaction done with the peak at Rf0.46 showed a fragment mass of 256. Evaporated solvent. Residue purified by (CH3CN/H2O 0-30%+TFA buffer )to get the desired product 1-(5-bromopyridin-3-yl)-4-methylpiperazine (92 mg, 21.27 %).

Here is a chemical reaction formula: Reactants are:amine:CC(C)(C)OC(=O)N1CCNCC1;aryl halide:C1=CSC(=C1)Cl, Reagents are:Solvent:CN(C)C=O;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3.C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3.C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3.C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3.[Pd];Base:CCN(CC)CC, and Products are 0:CC(C)(C)OC(=O)N1CCN(CC1)C2=CC=CS2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To a mixture of 2-chlorothiophene (0.248 mL, 2.68 mmol), tert-butyl piperazine-1-carboxylate (500 mg, 2.68 mmol), and TEA (1.123 mL, 8.05 mmol) in DMF (4 mL) was added Pd(Ph3P)4 (57.8 mg, .05 mmol). The reaction was allowed to heat at 95 °C for overnight. LCMS and TLC showed the starting material peak as well as the triphenyl phosphene ionized M+1 peak. The tryphenyl phosphene showed up at the same retention time as 2-chlorothiophene. No new peak was observed following the reaction so no purification techniques were run. MS (m+1) = not seen

Here is a chemical reaction formula: Reactants are:amine:C1=CC=C(C(=C1)CN)C(F)(F)F;aryl halide:C1=CC(=NC=C1C(=O)N)Cl, Reagents are:Base:CC(C)(C)[O-].[Na+];Solvent:COCCOC;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C1=CC=C(C(=C1)CNC2=NC=C(C=C2)C(=O)N)C(F)(F)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To a stirred solution of 6-chloronicotinamide (0.053 g, 0.34 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.021 g, 0.03 mmol), sodium 2-methylpropan-2-olate (0.065 g, 0.68 mmol) and diacetoxypalladium (7.60 mg, 0.03 mmol) in DME (1 mL) was added (2-(trifluoromethyl)phenyl)methanamine (0.095 mL, 0.68 mmol). The reaction mixture was subjected to microwave irradiation for 4h at 120 C. Only traces of product was observed. The crude product was dissolved in DMSO (2 mL) and purified using Fractionlynx I, (Xbridge Prep C18 5µm OBD 19x150 mm column), with 5 to 95% acetonitrile in 0.2% ammonia at pH 10. 6-(2-(trifluoromethyl)benzylamino)nicotinamide: 1.45 mg (1.5 %)

Here is a chemical reaction formula: Reactants are:amine:C1=CC(=CC(=C1)C(F)(F)F)CN;aryl halide:C1=CC(=NC=C1C(=O)N)Cl, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:CC(C)(C)[O-].[Na+];Solvent:COCCOC, and Products are 0:C1=CC(=CC(=C1)C(F)(F)F)CNC2=NC=C(C=C2)C(=O)N, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To a stirred solution of 6-chloronicotinamide (0.053 g, 0.34 mmol), sodium 2-methylpropan-2-olate (0.065 g, 0.68 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.020 g, 0.03 mmol) and diacetoxypalladium (7.60 mg, 0.03 mmol) in DME (1 mL) was added (3-(trifluoromethyl)phenyl)methanamine (0.049 mL, 0.34 mmol). The reaction was run in microwave at 120 C for 4h. only traces of product observed. Reaction wasted.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=NC=C1C(=O)N)Cl;amine:C1=CC(=CC=C1CN)C(F)(F)F, Reagents are:metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:COCCOC;Base:CC(C)(C)[O-].[Na+], and Products are 0:C1=CC(=CC=C1CNC2=NC=C(C=C2)C(=O)N)C(F)(F)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To a stirred solution of 6-chloronicotinamide (0.053 g, 0.34 mmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.021 g, 0.03 mmol), sodium 2-methylpropan-2-olate (0.065 g, 0.68 mmol) and diacetoxypalladium (7.60 mg, 0.03 mmol) in DME (1 mL) was added (4-(trifluoromethyl)phenyl)methanamine (0.097 mL, 0.68 mmol). The reaction was run in microwave at 100 °C for 4h. The compound was purified by preparative HPLC on a Kromasil C8 column (10 µm 250x20 ID mm) using a gradient of 51-55% acetonitrile in H2O/ACN/FA 95/5/0.2 buffer, over 25 minutes with a flow of 19 mL/min. The compounds were detected by UV at 270nm. 6-(4-(trifluoromethyl)benzylamino)nicotinamide (7.40 mg, 7.40 %) was obtained.

Here is a chemical reaction formula: Reactants are:aryl halide:COC1=C(C=C(C=C1)Br)C#N;amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC1=CC=CC=C1, and Products are 0:C[C@H](CNC1=CC(=C(C=C1)OC)C#N)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: PdOAc2 (0.529 g, 2.36 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (1.124 g, 2.36 mmol) were added in one portion to a degassed solution of 5-bromo-2-methoxybenzonitrile (5 g, 23.58 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (5.36 g, 28.30 mmol) and cesium carbonate (11.52 g, 35.37 mmol) in toluene (100 mL) at 20°C under nitrogen. The resulting suspension was stirred at 120 °C for 50 hours. The reaction mixture was diluted with EtOAc (150 mL) and water (150 mL) and the biphasic mixture was filtered through celite. The organic layer was separated and washed sequentially with water (150 mL) and saturated brine (150 mL). The organic layer was evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-5-(2-(tert- butyldimethylsilyloxy)propylamino)-2-methoxybenzonitrile (3.60 g, 47.6 %) as a pale yellow oil.

Here is a chemical reaction formula: Reactants are:aryl halide:COC1=C(C=C(C=C1)Br)C#N;amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C, Reagents are:Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C[C@H](CNC1=CC(=C(C=C1)OC)C#N)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Reaction carried PdOAc2 (0.476 g, 2.12 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (1.012 g, 2.12 mmol) were added in one portion to a degassed solution of 5-bromo-2-methoxybenzonitrile (4.50 g, 21.22 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (4.82 g, 25.47 mmol) and cesium carbonate (10.37 g, 31.83 mmol) in toluene (100 mL) at 20°C in a microwave vial. The microwave vial was sealed and the reaction was heated to 120 °C for 12 hours in the microwave reactor and cooled to RT. The reaction mixture was diluted with EtOAc (100 mL) and water (100 mL). The biphasic mixture was filtered through celite. The organic layer was separated and washed sequentially with water (100 mL) and saturated brine (100 mL). The organic layer was filtered and dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was evaporated and was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert- butyldimethylsilyloxy)propyl)-3-fluoroaniline (0.851 g, 61.4 %) as a orange oil.

Here is a chemical reaction formula: Reactants are:amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C;aryl halide:COC1=C(C=C(C=C1)Br)C#N, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1, and Products are 0:C[C@H](CNC1=CC(=C(C=C1)OC)C#N)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Trial reaction for PdOAc2 (0.021 g, 0.09 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.045 g, 0.09 mmol) were added in one portion to a degassed solution of 5-bromo-2-methoxybenzonitrile (0.200 g, 0.94 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (0.214 g, 1.13 mmol) and cesium carbonate (0.461 g, 1.41 mmol) in toluene (10 mL) at 20°C in a microwave vial. The reaction mixture was diluted with EtOAc (20 mL) and water (20 mL). The biphasic mixture was filtered through celite. The organic layer was separated and washed sequentially with water (50 mL) and saturated brine (50 mL). The organic layer was filtered and dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was evaporated and was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-5-(2-(tert- butyldimethylsilyloxy)propylamino)-2-methoxybenzonitrile (0.188 g, 62.2 %) as a orange oil. repated on a lager scale in RSL - See EN04063-90

Here is a chemical reaction formula: Reactants are:aryl halide:COC(=O)C1=NC=C(C=N1)Br;amine:CC(C)(C)OC(=O)N, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1, and Products are 0:CC(C)(C)OC(=O)NC1=CN=C(N=C1)C(=O)OC, please give me the reaction condition of this formula.

The condition of this chemical reaction is: The methyl 5-bromopyrimidine-2-carboxylate (1 g, 4.61 mmol), tert-butyl carbamate (0.756 g, 6.45 mmol), diacetoxypalladium (0.052 g, 0.23 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.267 g, 0.46 mmol), cesium carbonate (2.252 g, 6.91 mmol) and dioxane (15 mL) were placed and sealed into a microwave tube. The reaction was degased, purged with argon and heated to 90 °C (oil bath) over a period of 7 hours . The mixture was poured in water, extracted with ethyl acetate (x2). The organic phase was washed with brine, dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel 15-40µm eluting with 5 to 50% ethyl acetate in petroleum ether. The solvent was evaporated to dryness to afford methyl 5-(tert- butoxycarbonylamino)pyrimidine-2-carboxylate (0.710 g, 60.8 %) as a white solid.

Here is a chemical reaction formula: Reactants are:amine:CC(C)(C)OC(=O)N;aryl halide:COC(=O)C1=NC=C(C=N1)Br, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:CC(C)(C)OC(=O)NC1=CN=C(N=C1)C(=O)OC, please give me the reaction condition of this formula.

The condition of this chemical reaction is: The methyl 5-bromopyrimidine-2-carboxylate (4 g, 18.43 mmol), tert-butyl carbamate (3.02 g, 25.80 mmol), diacetoxypalladium (0.207 g, 0.92 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (1.066 g, 1.84 mmol), cesium carbonate (9.01 g, 27.65 mmol) and dioxane (50 mL) were placed and sealed into a microwave tube. The reaction was degased, purged with argon and heated to 90 °C (oil bath) over a period of 7 hours . The mixture was poured in water, extracted with ethyl acetate (x2). The organic phase was washed with brine, dried over magnesium sulfate and concentrated. The crude product was purified by flash chromatography on silica gel 15-40µm eluting with 5 to 50% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford methyl 5-(tert- butoxycarbonylamino)pyrimidine-2-carboxylate (3.00 g, 64.3 %) as a beige solid.

Here is a chemical reaction formula: Reactants are:aryl halide:CC1=CSC(=N1)C2CN(CC3=C(O2)N=C(C=C3)Cl)C;amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, Reagents are:Solvent:COCCOC;metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CC1=CSC(=N1)C2CN(CC3=C(O2)N=C(C=C3)NC4=NC(=C(C=C4)C5=CN(N=C5)C)OC)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To 8-chloro-4-methyl-2-(4-methylthiazol-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (207 mg, 0.70 mmol) in DME (3 mL) were 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (143 mg, 0.70 mmol), cesium carbonate (342 mg, 1.05 mmol), 2-(Dicyclohexylphosphino)biphenyl (24.53 mg, 0.07 mmol) and Palladium acetate (15.71 mg, 0.07 mmol) added. The reaction was heated to 110°C for 60 min under N2 atmosphere. The solids were filtered off and washed with DCM, the solvents were evaporated and the crude product was purified by silica flash chromatography using DCM : [DCM:MeOH:NH3 = 90:10:1] = 100:0 to 35:65 as gradient. The title compound was obtained as yellow foam.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:CC1=C(OC(=N1)N)C, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1, and Products are 0:CC1=C(OC(=N1)NC2=NC=CC(=C2)Cl)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Repeat of experiment in an attempt to improve isolated yield using different normal phase eluent system (isolation was problematic for ). Pd2(dba)3 (22.89 mg, 0.025 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (43.4 mg, 0.075 mmol), 2,4-dichloropyridine (148 mg, 1.00 mmol), cesium carbonate (652 mg, 2.00 mmol) and 4,5-dimethyloxazol-2-amine (112 mg, 1.00 mmol) were added to an oven dried microwave vial, the vial was capped and placed under an inert atmosphere, dioxane (4 mL) was added and the resulting mixture was heated to 140 °C for 1 h by microwave irradiation under a nitrogen atmosphere. The crude product was purified by flash silica chromatography, elution gradient 0 to 3% methanolic ammmonia (7 M) in DCM. Pure fractions were evaporated to dryness to afford P1 as a brown solid. The product was further purified by crystallisation from hot DCM/MeOH to afford N-(4-chloropyridin-2-yl)-4,5-dimethyloxazol-2-amine (34.0 mg, 15.20 %) as a beige solid. Conclusion: A relatively low yield of the desired product was isolated here, it may be possible to increase the above yield at higher temperature or by using excess amine as electron rich oxazoles are prone to decomposition.

Here is a chemical reaction formula: Reactants are:amine:CC1=C(OC(=N1)N)C;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1, and Products are 0:CC1=C(OC(=N1)NC2=NC=CC(=C2)Cl)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: To find out which substrates are efficient coupling partners, is there a robust link between how electron poor the substrate is and yield i.e. more electron poor aminooxazoles produce greater yields. Pd2(dba)3 (22.89 mg, 0.025 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (43.4 mg, 0.075 mmol), 2,4-dichloropyridine (148 mg, 1.00 mmol), cesium carbonate (652 mg, 2.00 mmol) and 4,5-dimethyloxazol-2-amine (112 mg, 1.00 mmol) were added to an oven dried microwave vial, the vial was capped and placed under an inert atmosphere, dioxane (4 mL) was added and the resulting mixture was heated to 140 °C for 1 h by microwave irradiation under a nitrogen atmosphere. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in heptane. Pure fractions were evaporated to dryness to afford N-(4-chloropyridin-2-yl)-4,5-dimethyloxazol-2-amine (34.0 mg, 15.20 %) as a pale yellow solid. Conclusion: The dimethyl substituted 2-aminooxazole (relatively electron rich) produces more coupled product than the unsubstituted 2-aminooxazole. Of the 2-aminooxazoles tested thus far the 4- and 5-ester substituted aminooxazoles are the most efficient coupling partners. Note: A run at T= 160 °C may be beneficial, an increase in yield was seen for the ester substituted 2-aminooxazole under these more forcing conditions.

Here is a chemical reaction formula: Reactants are:aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3;amine:CC1=CN(C=N1)C2=CN=C(C=C2)N, Reagents are:metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:COCCOC, and Products are 0:CC1=CN(C=N1)C2=CN=C(C=C2)NC3=NC4=C(CN(C[C@H](O4)C5=CC=CC=C5)C)C=C3, please give me the reaction condition of this formula.

The condition of this chemical reaction is: (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (129 mg, 0.47 mmol), 5-(4-methyl-1H-imidazol-1-yl)pyridin-2-amine (82 mg, 0.47 mmol), PALLADIUM(II) ACETATE (10.54 mg, 0.05 mmol), 2-(DICYCLOHEXYLPHOSPHINO)BIPHENYL (16.46 mg, 0.05 mmol) and Cs2CO3 (229 mg, 0.70 mmol) were weighed into a microwave vial which was capped and flushed with argon. DME (5 mL) was added and the mixture was heated to 100°C in a microwave apparatus for 2 h. The mixture was filtered and purified by column chromatography on Silica using gradient elution with increasing concentration of methanol, from 0 to 6 %, in dichloromethane to give(R)-4-methyl-N-(5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (69.5 mg, 35.9 %)

Here is a chemical reaction formula: Reactants are:aryl halide:CC1=CC(=NC2=C1CN(CC(O2)CC(F)(F)F)C)Cl;amine:CC1=CN(C=N1)C2=CN=C(C=C2)N, Reagents are:metal and ligand:C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:COCCOC, and Products are 0:CC1=CC(=NC2=C1CN(CC(O2)CC(F)(F)F)C)NC3=NC=C(C=C3)N4C=C(N=C4)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To 8-chloro-4,6-dimethyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (300 mg, 0.51 mmol) in DME (4 mL) were 5-(4-methyl-1H-imidazol-1-yl)pyridin-2-amine (89 mg, 0.51 mmol), cesium carbonate (249 mg, 0.76 mmol), 2-(Dicyclohexylphosphino)biphenyl (17.84 mg, 0.05 mmol) and Palladium acetate (11.43 mg, 0.05 mmol) added. The reaction was heated to 110°C for 3*90min. The solids were filtered of and washed with DCM and IPA and discarded. The solvents were evaporated and the crude product was purified using first flash chromatography, 0-7% MeOH in DCM and the prepHPLC yielding 4,6-dimethyl-N-(5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl)-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-amine (34.0 mg, 15.45 %)

Here is a chemical reaction formula: Reactants are:amine:CC(C)(C)OC(=O)N1CCNCC1;aryl halide:CCOC(=O)C1=CC2=C(O1)C=CC=C2Cl, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=CC2=C(C=CC=C2O1)N3CCN(CC3)C(=O)OC(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: tert-butyl piperazine-1-carboxylate (5.22 g, 28.04 mmol), ethyl 4-chlorobenzofuran-2-carboxylate (6.3 g, 28.04 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (1.337 g, 2.80 mmol), Tris(dibenzylideneacetone)dipalladium(0) (1.284 g, 1.40 mmol) and CESIUM CARBONATE (11.88 g, 36.46 mmol) were heated under argon to 95 °C 14:51:42 overnight, LC showed no s.m. EN03969-25-001. The mixture was allowed to cool to rt, diluted with EtOAc (35 mL) and filtered through a pad of Celite, washed with EtOAc (total of 100 mL). The filterate was collected and the solvent was removed by rotary evaporation. The crude product was treated with diisopropylether under stirring at rt for 4 days, the mixture was filterered and washed with diisopropylether. The diisopropyletherphase was concentrated to give 3.6 g. The solid was treated with MeOH under stirring at rt for 4 h, filtrated, washed with MeOH, still not clear solution. The solid was vacuumdried at 40 °C over night to give 7.6 g. The MeOH-mixture was filterered through a process K200 filter, the formed solution was concentrated to give 1.4 g. No pure product in any of the solids, were combined (12.6 g) and dissolved in CH2Cl2 and put on silica (200 g) using 1. CH2Cl2 (500 mL), 2. EtOAc (400 mL) as eluent. Fr. 5-6 were combined and concentrated to give EN03969-25-002 (10.6 g, 28.3 mmol, 101 %). To the brownish solid was added ether (40 mL) and the slurry was stirred at 35 °C for 5-10 min. The now grey solid was filtered off, rinsed with 4x20 mL ether and dried under vacuum at 30 °C o.n, yielding EN03969-25-003 (6.7 g, 17.89 mmol, 63.8 %). 44 mg of EN03969-25-003 was sent to **** at Analytical Services and OA Support team **** for purity-assay (95 %), see report. EN03969-25-003 was delivered to CM in can: **32649089.**

Here is a chemical reaction formula: Reactants are:amine:C1CNCCN1;aryl halide:C1=CC(=C(C=C1Cl)Br)C#N, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:C1CN(CCN1)C2=C(C=CC(=C2)Cl)C#N, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Tris(dibenzylideneacetone)dipalladium (0) (43.4 mg, 0.05 mmol) and rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (59.0 mg, 0.09 mmol) were added to a mixture of 2-bromo-4-chlorobenzonitrile (205 mg, 0.95 mmol), Cesium carbonate (463 mg, 1.42 mmol) and Piperazine (163 mg, 1.89 mmol) in dioxane (3 mL). Reaction vessel was placed in an oil bath set to 90 °C 2.45pm. LCMS o/n shows large product peak (222). Cooled, filtered through a silica plug, washing with EtOAc until filtrate is clear. Crude NMR is very messy, target deprioritized. Discarded.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=C(C=C1F)Br)C#N;amine:C1CNCCN1, Reagents are:metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1CN(CCN1)C2=C(C=CC(=C2)F)C#N, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Tris(dibenzylideneacetone)dipalladium (0) (57.2 mg, 0.06 mmol) and rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (78 mg, 0.12 mmol) were added to a mixture of 2-bromo-4-fluorobenzonitrile (250 mg, 1.25 mmol), Cesium carbonate (611 mg, 1.87 mmol) and Piperazine (215 mg, 2.50 mmol) in dioxane (3 mL). Reaction vessel was placed in an oil bath at 90 °C 4pm. LCMS o/n shows several peaks. Larger peak corresponding to displacement of F by piperazine (MW266) than for desired product (205). Discarded

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Br;amine:C1=COC(=N1)N, Reagents are:Base:C1=CC=C(C=C1)[O-].[Na+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:C1=CN=C(C=C1Cl)NC2=NC=CO2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Improve yield of the desired product starting from the bromoaryl compound. To a flask containing 2-bromo-4-chloropyridine (196 mg, 1.02 mmol), sodium phenolate (177 mg, 1.52 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (11.63 mg, 0.01 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (17.64 mg, 0.03 mmol) (Xantphos), was added degassed dioxane (4 mL) and the mixture allowed to stir under nitrogen atmosphere for 5 min. To this solution was added oxazol-2-amine (94 mg, 1.12 mmol) and the reaction mixture was heated to 170 °C for 2 h under microwave irradiation. Methanol was added to the crude reaction mixture together with silica (2 g), the solvent was removed under reduced pressure and the remaining residue was placed in dry load tube prior to chromatography. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in heptane. Pure fractions were evaporated to dryness to afford N-(4-chloropyridin-2-yl)oxazol-2-amine (1.000 mg, 0.503 %) as a beige solid. Conclusion: Trace amount of the desired product isolated.

Here is a chemical reaction formula: Reactants are:amine:C1=COC(=N1)N;aryl halide:C1=CN=C(C=C1Cl)Br, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1, and Products are 0:C1=CN=C(C=C1Cl)NC2=NC=CO2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: To find out if the 2-bromopyridine is a more efficient coupling partner than the chloro analogue. Pd2(dba)3 (22.89 mg, 0.025 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (43.4 mg, 0.075 mmol), 2-bromo-4-chloropyridine (192 mg, 1.00 mmol), cesium carbonate (652 mg, 2.00 mmol) and oxazol-2-amine (84 mg, 1.00 mmol) were added to an oven dried microwave vial, the vial was capped and placed under an inert atmosphere, dioxane (4 mL) was added and the resulting mixture was heated at 140 °C for 1 h by microwave irradiation under a nitrogen atmosphere. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in heptane. Pure fractions were evaporated to dryness to afford N-(4-chloropyridin-2-yl)oxazol-2-amine (15.00 mg, 7.67 %) as a white solid. Conclusion: A slightly improved yield of the desired product was formed with respect to the 2,4-dichloropyridine substrate, however the difference could not be taken to be significant.

Here is a chemical reaction formula: Reactants are:amine:C1=CC(=CC(=C1)[N+](=O)[O-])N;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C1=CC(=CC(=C1)[N+](=O)[O-])NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 3-Nitroaniline (140 mg, 1.01 mmol), 2,4-dichloropyridine (150 mg, 1.01 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (70.4 mg, 0.12 mmol) and cesium carbonate (660 mg, 2.03 mmol) were stirred in dioxane (5 mL). The mixture was purged with nitrogen for 10 minutes. Palladium(II) acetate (22.76 mg, 0.10 mmol) was added and the mixture heated at 100 °C for 1.5h. The mixture was cooled, filtered and concentrated. The crude product was purified by flash silica chromatography, eluting with 1% MeOH in DCM. Pure fractions were evaporated to dryness to afford 4-chloro-N-(3-nitrophenyl)pyridin-2-amine (121 mg, 47.8 %) as a yellow solid.

Here is a chemical reaction formula: Reactants are:aryl halide:CN1CCN(CC1)C2=C(C=C(C(=C2)OC)N)Br;amine:CC(C)(C)OC(=O)N, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CC(C)(C)OC(=O)NC1=C(C=C(C(=C1)N)OC)N2CCN(CC2)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To a suspension of 5-bromo-2-methoxy-4-(4-methylpiperazin-1-yl)aniline (50 mg, 0.17 mmol) in dioxane (4 mL) was added tert-butyl carbamate (24.39 mg, 0.21 mmol), cesium carbonate (81 mg, 0.25 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (19.27 mg, 0.03 mmol). The resulting suspension was degassed and Palladium(II) acetate (3.74 mg, 0.02 mmol) was added. The mixture was degassed and stirred at 120 °C for 2 hours in the CEM microwave, then allowed to cool to ambient temperature. The reaction was incomplete so further cesium carbonate (81 mg, 0.25 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (19.27 mg, 0.03 mmol) and diacetoxyzinc (30.6 mg, 0.17 mmol) were added and the mixture was degassed. Further Palladium(II) acetate (3.74 mg, 0.02 mmol) was added, and the mixture was degassed and stirred at 130 °C for 1 hour in the CEM microwave, then allowed to cool to amibient temperature. TLC (10% MeOH in DCM + 1% cNH3 (aq)) suggests bromo SM has been consumed but no evidence of desired product having been formed. UPLC shows only oxidised xantphos. Reaction stopped

Here is a chemical reaction formula: Reactants are:aryl halide:CC1=C(C=C(C=C1)NC(=O)C2=CC3=C(C=C2)OCCO3)NC(=O)C4=CN=C(C=C4)Cl;amine:CN1CCC(CC1)OC2=CC=CC(=C2)N, Reagents are:Base:CC(C)(C)[O-].[Na+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:CC1=CC=CC=C1, and Products are 0:CC1=C(C=C(C=C1)NC(=O)C2=CC3=C(C=C2)OCCO3)NC(=O)C4=CN=C(C=C4)NC5=CC(=CC=C5)OC6CCN(CC6)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A mixture of 6-chloro-N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)nicotinamide (50 mg, 0.12 mmol),3-(1-methylpiperidin-4-yloxy)aniline (36.5 mg, 0.18 mmol),(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (4.10 mg, 7.08 µmol),TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (3.24 mg, 3.54 µmol),sodium 2-methylpropan-2-olate (17.01 mg, 0.18 mmol) in toluene (2 mL)/IPA (0.500 mL)was degassed with nitrogen and heated at reflux for 18 hours.The reaction mixture was diluted with EtOAc (100 mL), and washed sequentially with water (100 mL), The organic layer was dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% MeOH/7MNH3 in EtOAc. lcms still showed 30% unreacted aniline. Fractions evaporated.The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)-6-(3-(1-methylpiperidin-4-yloxy)phenylamino)nicotinamide (23.00 mg, 32.8 %) as a cream solid.

Here is a chemical reaction formula: Reactants are:amine:CN(C)CC1=CC(=CC=C1)N;aryl halide:CC1=C(C=C(C=C1)NC(=O)C2=CC3=C(C=C2)OCCO3)NC(=O)C4=CN=C(C=C4)Cl, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:CC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1, and Products are 0:CC1=C(C=C(C=C1)NC(=O)C2=CC3=C(C=C2)OCCO3)NC(=O)C4=CN=C(C=C4)NC5=CC=CC(=C5)CN(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A mixture of 6-chloro-N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)nicotinamide (50 mg, 0.12 mmol),3-((dimethylamino)methyl)aniline (26.6 mg, 0.18 mmol),(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (4.10 mg, 7.08 µmol),TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (3.24 mg, 3.54 µmol),sodium 2-methylpropan-2-olate (17.01 mg, 0.18 mmol) in toluene (2 mL)/IPA (0.500 mL)was degassed with nitrogen and heated at reflux for 18 hours.The reaction mixture was filtered and filtered solid washed with ethyl acetate. The organic filtrate was washed with water (50ml), and organic layer dried over Na2SO4, filtered and evaporated. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)-6-(3-((dimethylamino)methyl)phenylamino)nicotinamide (24.60 mg, 38.8 %) as a cream solid.

Here is a chemical reaction formula: Reactants are:amine:CN(C)C1CCN(C1)C2=CC=CC(=C2)N;aryl halide:CC1=C(C=C(C=C1)NC(=O)C2=CC3=C(C=C2)OCCO3)NC(=O)C4=CN=C(C=C4)Cl, Reagents are:Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CC1=C(C=C(C=C1)NC(=O)C2=CC3=C(C=C2)OCCO3)NC(=O)C4=CN=C(C=C4)NC5=CC(=CC=C5)N6CCC(C6)N(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A mixture of 6-chloro-N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)nicotinamide (70 mg, 0.17 mmol),[Reactants],(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (5.73 mg, 9.91 µmol),TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (4.54 mg, 4.95 µmol),sodium 2-methylpropan-2-olate (23.81 mg, 0.25 mmol) in toluene (4 mL)/IPA (1.000 mL)was degassed with nitrogen and heated at reflux for 18 hours.The reaction mixture was filtered and filtered solid washed with ethyl acetate. The organic filtrate was washed with water (50ml), and organic layer dried over Na2SO4, filtered and evaporated.The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamido)-2-methylphenyl)-6-(3-(3-(dimethylamino)pyrrolidin-1-yl)phenylamino)nicotinamide (10.00 mg, 10.22 %) as a cream solid.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:CC1=COC(=N1)N, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CC1=COC(=N1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: To find out which substrates are efficient coupling partners, is there a robust link between how electron poor the substrate is and yield i.e. more electron poor aminooxazoles produce greater yields. Pd2(dba)3 (22.89 mg, 0.025 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (43.4 mg, 0.075 mmol), 2,4-dichloropyridine (148 mg, 1.00 mmol), cesium carbonate (652 mg, 2.00 mmol) and 4-methyloxazol-2-amine (98 mg, 1.00 mmol) were added to an oven dried microwave vial, the vial was capped and placed under an inert atmosphere, dioxane (4 mL) was added and the resulting mixture was heated to 140 °C for 1 h by microwave irradiation under a nitrogen atmosphere. Dichloromethane (10 mL) was added to the crude reaction mixture and the mixture was adsorbed onto silica gel. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in heptane. Pure fractions were evaporated to dryness to afford N-(4-chloropyridin-2-yl)-4-methyloxazol-2-amine (59.0 mg, 28.1 %) as a cream solid. Note: a further 34 mg of impure product came off the column early and so the yield for this reaction is probably closer to 35% had the purification been efficient. Conclusion: Somewhat surprisingly the methyl substituted amino-oxazole gave significant amounts of coupled product. It appears that certain moderately elctron rich substrates may also undergo relatively efficient coupling.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=NC=C1Br)Br;amine:CO[C@@H]1CCNC1, Reagents are:Base:CC(C)(C)[O-].[Na+];metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:CC1=CC=CC=C1, and Products are 0:CO[C@@H]1CCN(C1)C2=CC(=CN=C2)Br, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A mixture of 3,5-dibromopyridine (0.644 g, 2.72 mmol), (R)-3-methoxypyrrolidine (0.25 g, 2.47 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (0.045 g, 0.05 mmol), sodium 2-methylpropan-2-olate (0.356 g, 3.71 mmol) and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.077 g, 0.12 mmol) in degassed toluene (7.5 ml) was sealed into a microwave tube and stirred for 16 hours at 90 °C. The reaction was completed. After cooling, an aqueous solution of Na2CO3 was added. Extraction with DCM (twice). The organic layers were dried over MgSO4 and evaporated _in vacuo_ to give the crude product as an orange oil. PBO-04062-54-01 It was purified by chromatography (Merck cartridge SVF D26 - SI60 15-40 µm - 30 g) on silica gel eluting with EtOAc 0 to 25% in petroleum ether. Pure collected fractions were evaporated to afford (R)-3-bromo-5-(3-methoxypyrrolidin-1-yl)pyridine (0.325 g, 51.1 %) as a yellow oil. PBO-04062-54-02

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=C(C=C1)COC2=C(C=C(C=C2)Br)F;amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C[C@H](CNC1=CC(=C(C=C1)OCC2=CC=CC=C2)F)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: PdOAc2 (1.198 g, 5.34 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (2.54 g, 5.34 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (15.00 g, 53.36 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (12.63 g, 66.70 mmol) and cesium carbonate (26.1 g, 80.04 mmol) in toluene (150 mL) at 120°C under nitrogen. The resulting suspension was stirred at 120 °C for 16 hours. The reaction was incomplete so the reaction mixture was stirred for a further 24 hours at 120°C. The reaction mixture was cooled and diluted with EtOAc (150 mL) and water (150 mL). The biphasic mixture was filtered through celite. The organic layer was separated and washed sequentially with water (150 mL) and saturated brine (150 mL). The organic layer was filtered and dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was evaporated and was purified by flash silica chromatography*, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)propyl)-3-fluoroaniline (11.7 g, 30.0 mmol, 56.3 %) as a orange oil. Fractions that contained small amounts of impurities were also combined and were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert- butyldimethylsilyloxy)propyl)-3-fluoroaniline (2.5 g, 6.42 mmol, 12.03 %) as a dark orange oil.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=C(C=C1)COC2=C(C=C(C=C2)Br)F;amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1, and Products are 0:C[C@H](CNC1=CC(=C(C=C1)OCC2=CC=CC=C2)F)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: PdOAc2 (0.080 g, 0.36 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.170 g, 0.36 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (1 g, 3.56 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (0.674 g, 3.56 mmol) and cesium carbonate (1.739 g, 5.34 mmol) in toluene (20 mL) at 120°C under nitrogen. The resulting suspension was stirred at 120 °C for 16 hours. The reaction mixture was diluted with EtOAc (20 mL) and water (20 mL). The biphasic mixture was filtered through celite. The organic layer was separated and washed sequentially with water (50 mL) and saturated brine (50 mL). The organic layer was filtered and dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was evaporated and was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert- butyldimethylsilyloxy)propyl)-3-fluoroaniline (0.851 g, 61.4 %) as a orange oil.

Here is a chemical reaction formula: Reactants are:amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C;aryl halide:C1=CC=C(C=C1)COC2=C(C=C(C=C2)Br)F, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:C1COCCO1, and Products are 0:C[C@H](CNC1=CC(=C(C=C1)OCC2=CC=CC=C2)F)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: PdOAc2 (0.080 g, 0.36 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.170 g, 0.36 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (1 g, 3.56 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (0.808 g, 4.27 mmol) and cesium carbonate (1.739 g, 5.34 mmol) in anhydrous dioxane (20 mL) at 20°C in a microwave vial. The microwave vial was sealed and the reaction was heated to 120 °C for 10 hours in the microwave reactor and cooled to RT. LCMS indicates mainly starting material **** No further action was taken.

Here is a chemical reaction formula: Reactants are:amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C;aryl halide:C1=CC=C(C=C1)COC2=C(C=C(C=C2)Br)F, Reagents are:Solvent:CC1=CC=CC=C1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C[C@H](CNC1=CC(=C(C=C1)OCC2=CC=CC=C2)F)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: PdOAc2 (0.799 g, 3.56 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (1.696 g, 3.56 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (10.00 g, 35.57 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (8.08 g, 42.69 mmol) and cesium carbonate (17.39 g, 53.36 mmol) in toluene (150 mL) at 20°C under nitrogen. The resulting suspension was stirred at 120 °C for 35 hours. The reaction mixture was diluted with EtOAc (150 mL) and water (150 mL) and the biphasic mixture was filtered through celite. The organic layer was separated and washed sequentially with water (150 mL) and saturated brine (150 mL). The organic layer was evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)propyl)-3-fluoroaniline (9.38 g, 67.7 %) as a orange oil. ****

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=C(C=C1)COC2=C(C=C(C=C2)Br)F;amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C[C@H](CNC1=CC(=C(C=C1)OCC2=CC=CC=C2)F)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: PdOAc2 (1.198 g, 5.34 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (2.54 g, 5.34 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (15.00 g, 53.36 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (12.63 g, 66.70 mmol) and cesium carbonate (26.1 g, 80.04 mmol) in toluene (200 mL) at 120°C under nitrogen. The resulting suspension was stirred at 120 °C for 16 hours under nitrogen. The reaction was incomplete so the reaction mixture was stirred for a further 24 hours at 120°C. The reaction mixture was cooled and diluted with EtOAc (150 mL) and water (150 mL). The biphasic mixture was filtered through celite. The organic layer was separated and washed sequentially with water (150 mL) and saturated brine (150 mL). The organic layer was filtered and dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography*, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)propyl)-3-fluoroaniline (12.2 g, 31.3 mmol, 58.7 %) as a orange oil. Fractions that contained small amounts of impurities were also combined and were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert- butyldimethylsilyloxy)propyl)-3-fluoroaniline (2.05 g, 5.26 mmol, 9.86 %) as a dark orange oil.

Here is a chemical reaction formula: Reactants are:amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C;aryl halide:C1=CC=C(C=C1)COC2=C(C=C(C=C2)Br)F, Reagents are:Solvent:CC1=CC=CC=C1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C[C@H](CNC1=CC(=C(C=C1)OCC2=CC=CC=C2)F)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: PdOAc2 (0.040 g, 0.18 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.085 g, 0.18 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (0.500 g, 1.78 mmol), [Reactants] and cesium carbonate (0.869 g, 2.67 mmol) in toluene (15 mL) at 20°C in a microwave vial. The microwave vial was sealed and the reaction was heated to 120 °C for 12 hours in the microwave reactor and cooled to RT. The reaction mixture was diluted with EtOAc (50 mL), and washed sequentially with water (50 mL) and saturated brine (50 mL). The organic layer was filtered and dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was taken up in DCM (20 mL) and an isoluble white solid EN04063-43-1 (401 mg) was filtered off (not product). The filtrate was evaporated and was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)propyl)-3-fluoroaniline (0.482 g, 69.6 %) as a yellow oil.

Here is a chemical reaction formula: Reactants are:amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C;aryl halide:C1=CC=C(C=C1)COC2=C(C=C(C=C2)Br)F, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC1=CC=CC=C1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C[C@H](CNC1=CC(=C(C=C1)OCC2=CC=CC=C2)F)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: PdOAc2 (0.799 g, 3.56 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (1.696 g, 3.56 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (10.00 g, 35.57 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (8.08 g, 42.69 mmol) and cesium carbonate (17.39 g, 53.36 mmol) in toluene (150 mL) at 120°C under nitrogen. The resulting suspension was stirred at 120 °C for 16 hours. The reaction was incomplete so the reaction mixture was stirred for a further 24 hours at 120°C. The reaction mixture was diluted with EtOAc (150 mL) and water (150 mL). The biphasic mixture was filtered through celite. The organic layer was separated and washed sequentially with water (150 mL) and saturated brine (150 mL). The organic layer was filtered and dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was evaporated and was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)propyl)-3-fluoroaniline (8.98 g, 64.8 %) as a orange oil.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=C(C=C1)COC2=C(C=C(C=C2)Br)F;amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C, Reagents are:Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C[C@H](CNC1=CC(=C(C=C1)OCC2=CC=CC=C2)F)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: PdOAc2 (0.399 g, 1.78 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.848 g, 1.78 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (5.00 g, 17.79 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (3.37 g, 17.79 mmol) and cesium carbonate (8.69 g, 26.68 mmol) in toluene (120 mL) at 20°C in a microwave vial. The microwave vial was sealed and the reaction was heated to 120 °C for 10 hours in the microwave reactor and cooled to RT. **** Split into 5 x 20 ml mw vials such as in each was: PdOAc2 (0.080 g, 0.36 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.170 g, 0.36 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (1.000 g, 3.56 mmol), Reactant 2 (1.143 g, 3.56 mmol) and cesium carbonate (1.739 g, 5.34 mmol) in toluene (20 mL) at 20°C in a microwave vial. The microwave vial was sealed and the reaction was heated to 120 °C for 10 hours in the microwave reactor and cooled to RT. **** The reaction was incomplete so the reaction was heated to 120 °C for 10 hours in the microwave reactor and cooled to RT. **** The reaction mixtures were combined and diluted with EtOAc (100 mL), and washed sequentially with water (100 mL) and saturated brine (100 mL). The organic layer was filtered and dried over Na2SO4. The filtrate was washed sequentially with water (100 mL), and saturated brine (100 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert- butyldimethylsilyloxy)propyl)-3-fluoroaniline (5.10 g, 73.6 %) as a orange oil.

Here is a chemical reaction formula: Reactants are:amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C;aryl halide:C1=CC=C(C=C1)COC2=C(C=C(C=C2)Br)F, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C[C@H](CNC1=CC(=C(C=C1)OCC2=CC=CC=C2)F)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: PdOAc2 (0.799 g, 3.56 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (1.696 g, 3.56 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (10.00 g, 35.57 mmol), 1-(benzyloxy)-4-bromo-2-fluorobenzene (10.00 g, 35.57 mmol) and cesium carbonate (17.39 g, 53.36 mmol) in toluene (100 mL) at 20°C in a microwave vial. The microwave vial was sealed and the reaction was heated to 120 °C for 10 hours in the microwave reactor and cooled to RT. _Split into 10 x 20 ml mw vials such as in each was:_ PdOAc2 (0.080 g, 0.36 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.170 g, 0.36 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (1.000 g, 3.56 mmol), 2-(tert- butyldimethylsilyloxy)ethanamine (0.832 g, 3.56 mmol) and cesium carbonate (1.739 g, 5.34 mmol) in toluene (20 mL) at 20°C in a microwave vial. The microwave vial was sealed and the reaction was heated to 120 °C for 10 hours in the microwave reactor and cooled to RT. The reaction mixtures were combined and diluted with EtOAc (150 mL) and water (150 mL). The biphasic mixture was filtered through celite. The organic layer was separated and washed sequentially with water (150 mL) and saturated brine (150 mL). The crude product was evaporated and was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert- butyldimethylsilyloxy)propyl)-3-fluoroaniline (10.10 g, 72.9 %) as a orange oil.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=C(C=C1)COC2=C(C=C(C=C2)Br)F;amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC1=CC=CC=C1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C[C@H](CNC1=CC(=C(C=C1)OCC2=CC=CC=C2)F)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: PdOAc2 (0.124 g, 0.55 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.263 g, 0.55 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (1.550 g, 5.51 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (1.044 g, 5.51 mmol) and cesium carbonate (2.69 g, 8.27 mmol) in toluene (20 mL) at 20°C in a microwave vial. The microwave vial was sealed and the reaction was heated to 120 °C for 10 hours in the microwave reactor and cooled to RT. **** The reaction was incomplete so the reaction was heated to 120 °C for 2 hours in the microwave reactor and cooled to RT. The reaction was incomplete and further PdOAc2 (0.124 g, 0.55 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.263 g, 0.55 mmol) was added and the suspension was stirred at 120 °C for a further 6 hours in the microwave reactor and cooled to RT. The reaction mixture was diluted with EtOAc (50 mL), and washed sequentially with water (50 mL) and saturated brine (50 mL). The organic layer was filtered and dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was taken up in DCM (20 mL) and an isoluble white solid EN04063-48-1 (1.45 g, 3.72 mmol, 67.5 %) was filtered off (not product). The filtrate was evaporated and was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)propyl)-3-fluoroaniline (1.450 g, 67.5 %) as a yellow oil. **** Reaction is slow if done on 1.5g scale in a 20 ml reaction vial. Next time do 1g reaction per 20 ml vial. See EN04063-50

Here is a chemical reaction formula: Reactants are:amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C;aryl halide:C1=CC=C(C=C1)COC2=CC=C(C=C2)Br, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC1=CC=CC=C1, and Products are 0:C[C@H](CNC1=CC=C(C=C1)OCC2=CC=CC=C2)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Palladium(II) acetate (0.427 g, 1.90 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.906 g, 1.90 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromobenzene (5 g, 19.00 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (4.32 g, 22.80 mmol) and Cesium carbonate (2.281 mL, 28.50 mmol) in toluene (75 mL) at 20°C under nitrogen. The resulting suspension was stirred at 120°C for 72 hours. The reaction mixture was diluted with EtOAc (150mL) and water (150mL) and the biphasic mixture was filtered through celite. The organic layer was seperated and washed sequentially with water (150mL) and saturated brine (150mL). The organic layer was evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)propyl)aniline (4.60 g, 65.1 %) as an orange oil.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=C(C=C1)COC2=CC=C(C=C2)Br;amine:C[C@H](CN)O[Si](C)(C)C(C)(C)C, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C[C@H](CNC1=CC=C(C=C1)OCC2=CC=CC=C2)O[Si](C)(C)C(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Reaction carried out as follows: PdOAc2 (0.768 g, 3.42 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (1.631 g, 3.42 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromobenzene (9.00 g, 34.20 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (7.77 g, 41.04 mmol) and cesium carbonate (16.72 g, 51.31 mmol) in toluene (200 mL) at 20°C in a 300 ml Milestone microwave reactor. The microwave reactor was sealed and the reaction was heated to 120 °C for 10 hours in and cooled to RT. LCMS indicated some product but mainly sm so another aliquot of catalyst was added and put back on for 10 hours at 130°C. LCMS-2 indicated complete reaction. Handed back to chemist for work-up. Workup The reaction mixture was diluted with EtOAc (100 mL) and was filtered. The solid (inorganics and catalyst) was washed with ethylacete (50 mL). The filtrates were combined and washed with water (1 x 150 mL) and brine (1 x 150 mL). The crude product was evaporated and was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert- butyldimethylsilyloxy)propyl)aniline (2.400 g, 18.88 %) as a orange oil.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:C1=C(N=C(O1)N)C(F)(F)F, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1, and Products are 0:C1=CN=C(C=C1Cl)NC2=NC(=CO2)C(F)(F)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Repeat of EN04881-41 to get pure sample of product in potentially higher isolated yield. cesium carbonate (652 mg, 2.00 mmol), Pd2(dba)3 (22.89 mg, 0.025 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (43.4 mg, 0.075 mmol), 4-(trifluoromethyl)oxazol-2-amine (152 mg, 1.00 mmol) and 2,4-dichloropyridine (148 mg, 1.00 mmol) were added to an oven dried microwave vial, the vial was capped and placed under an inert atmosphere, dioxane (4 mL) was added and the resulting mixture was heated at 140 °C for 1 h by microwave irradiation under a nitrogen atmosphere. Dichloromethane (10 mL) was added to the reaction mixture and the crude reaction mixture was adsorbed onto silica gel. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in heptane. Pure fractions were evaporated to dryness to afford N-(4-chloropyridin-2-yl)-4-(trifluoromethyl)oxazol-2-amine (46.0 mg, 17.45 %) as a pale yellow solid. Regioisomeric assignment confirmed by NOESY experiment (see sample P1 analytical data for details).

Here is a chemical reaction formula: Reactants are:amine:C1CNC(=O)CN1;aryl halide:C1=CC(=CC=C1F)Br, Reagents are:Solvent:CC1=CC=CC=C1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:CC(C)(C)[O-].[Na+], and Products are 0:C1CN(CC(=O)N1)C2=CC=C(C=C2)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: diacetoxypalladium (11.21 mg, 0.05 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (28.9 mg, 0.05 mmol) were dissolved in toluene (0.5 mL) under nitrogen. Stirred at 50C for 30min. sodium 2-methylpropan-2-olate (96 mg, 1.00 mmol) and piperazin-2-one (50 mg, 0.50 mmol) were added to a second microwave vial and inerted with nitrogen. 1-bromo-4-fluorobenzene (0.055 mL, 0.50 mmol) and toluene (0.500 mL) were added. The catalyst solution wad added to the reaction mixture and the resulting solution was stirred at 100C for 1h in the microwave. No reaction. Then 150C for 1h, still no reaction. The reaction was discarded.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=CC=C1F)Br;amine:C1CNC(=O)CN1, Reagents are:Solvent:CC1=CC=CC=C1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:CC(C)(C)[O-].[Na+], and Products are 0:C1CN(CC(=O)N1)C2=CC=C(C=C2)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: diacetoxypalladium (11.21 mg, 0.05 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (28.9 mg, 0.05 mmol) were dissolved in toluene (0.5 mL) under nitrogen. Stirred at 50C for 30min. sodium 2-methylpropan-2-olate (96 mg, 1.00 mmol) and piperazin-2-one (50 mg, 0.50 mmol) were added to a second microwave vial and inerted with nitrogen. 1-bromo-4-fluorobenzene (0.110 mL, 1.00 mmol) and toluene (0.500 mL) were added. The catalyst solution wad added to the reaction mixture and the resulting solution was stirred at 100C for 1h in the microwave. No reaction. Heated to 150C for 1h, still no reaction, the reaction was discarded.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=CC=C1F)Br;amine:C1CN(CCN1)CC2=CC=CC=C2, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+], and Products are 0:C1CN(CCN1CC2=CC=CC=C2)C3=CC=C(C=C3)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: diacetoxypalladium (12.74 mg, 0.06 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (32.8 mg, 0.06 mmol) were suspended in toluene (0.5 mL) under N2. Heated to 50C for 30 min (microwave). sodium 2-methylpropan-2-olate (109 mg, 1.13 mmol) was suspended in toluene (0.500 mL) under N2. 1-benzylpiperazine (0.099 mL, 0.57 mmol) and 1-bromo-4-fluorobenzene (0.093 mL, 0.85 mmol) were added, followed by the catalyst solution. Heated to 100C for 2h in the microwave (high abs), then rt over night. The product was purified on silica (0-25% EtOAc/heptane) Yield: 1-benzyl-4-(4-fluorophenyl)piperazine (115 mg, 75.0 %)

Here is a chemical reaction formula: Reactants are:amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC;aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC(C)(C)P(C(C)(C)C)C(C)(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CN1C[C@H](OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5=CC=CC=C5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Charged a standard microwave vial with a mixture of 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (100 mg, 0.49 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (135 mg, 0.49 mmol), cesium carbonate (239 mg, 0.73 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.42 mg, 0.02 mmol), Tri-tert- butylphosphonium tetrafluoroborate (14.21 mg, 0.05 mmol), and 1,2-dimethoxyethane. The atmosphere was inerted through vacuum-nitrogen cycles and the contents were heated at 120 °C for a period of 30 min. LCMS indicates reaction progression is less than 10%. Reaction aborted. Not progressed.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:CCOC(=O)C1=CN=C(O1)N, Reagents are:Base:C(=O)([O-])[O-].[K+].[K+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:COC1=CC=CC=C1, and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Repeat of optimised conditions found in process research and devellopment screen for an isolated yield. An activated catalyst solution was prepared by adding TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (61.3 mg, 0.07 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (77 mg, 0.13 mmol) to an oven-dried microwave vial. The vial was then capped and purged with nitrogen and anisole (1 mL) was added. The solution was stirred at 50°C for 40 mins, then 90°C for 15 mins (activated catalyst solution, Soln. 1). To another oven-dried microwave vial was added potassium carbonate (126 mg, 0.91 mmol), ethyl 2-aminooxazole-5-carboxylate (190 mg, 1.22 mmol) and 2,4-dichloropyridine (90 mg, 0.61 mmol) and the vial was capped and purged with nitrogen. anisole (1.35 mL) and the activated catalyst solution (0.45 mL Soln. 1 from above) were added (this corresponds to a catalyst loading of 10% Pd) and the vessel was heated to 90 °C for 16 h. LCMS of the crude reaction mixture showed the presence of a significant amount of amine starting material (Rt=0.95 min) as well as some 2,4-dichloropyridine starting material (Rt=1.75 min) together with a small amount of the desired product (Rt= 2.08). The mass corresponding to the double addition product was not observed. Conclusion: Reaction produced a small amount of the desired product but mainly starting material remained.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:CCOC(=O)C1=CN=C(O1)N, Reagents are:Base:C(=O)([O-])[O-].[K+].[K+];Solvent:COC1=CC=CC=C1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Repeat of optimised conditions found in process research and devellopment screen for an isolated yield. An activated catalyst solution was prepared by adding TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (61.3 mg, 0.07 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (77 mg, 0.13 mmol) to an oven-dried microwave vial. The vial was then capped, purged with nitrogen and anisole (1 mL) (degassed) was added. The solution was stirred at 50°C for 40 mins, then 90°C for 15 mins (activated catalyst solution, Soln. 1). To another oven-dried microwave vial was added potassium carbonate (126 mg, 0.91 mmol), ethyl 2-aminooxazole-5-carboxylate (190 mg, 1.22 mmol) and 2,4-dichloropyridine (90 mg, 0.61 mmol) and the vial was capped and purged with nitrogen. anisole (1.6 mL) and the activated catalyst solution (0.45 mL of Soln. 1 from above) were added (this corresponds to a catalyst loading of 10% Pd). The vessel was then heated to 120°C for 16 h. LCMS and TLC of the crude reaction mixture showed none of the desired product to be present. Some of the amine starting material appears to be present and none of the 2,4-dichloropyridine remains. The mass for the double addition product (addition at the 2- and 4-positions) is present, but co-elutes with the reaction solvent anisole and is not quantifiable as a result. Conclusion: This is a somewhat surprising result, based on the fact that the previous reaction (EN05378-17) results in the formation of significant coupled product. These reaction conditions are apparently not suitable for the coupling of the ester substituted 2-aminooxazole.

Here is a chemical reaction formula: Reactants are:amine:CCOC(=O)C1=CN=C(O1)N;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1, and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Peparation of the above coupled product on a larger scale for hydrolysis-protodecarboxylation study. To an oven-dried microwave vial was added ethyl 2-aminooxazole-5-carboxylate (546 mg, 3.50 mmol), 2,4-dichloropyridine (0.378 mL, 3.50 mmol), cesium carbonate (2279 mg, 6.99 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (80 mg, 0.09 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (152 mg, 0.26 mmol) and the vial was capped and purged with nitrogen. dioxane (18 mL) (degassed) was added and the reaction mixture was heated to 160 °C for 1 h under microwave irradiation. LCMS of the crude reaction mixture shows the required product to be the major product together with an isomer of the same mass (Rt= 1.91), the ratio of the desired product to this isomeric product being circa 5:1. LCMS also shows that a small amount of the 2-aminooxazole ester starting material remains (Rt= 0.99 min) and so the reaction with this particular substrate may benefit from slightly longer reaction times, maybe 90 mins. A small amount of the coupled and decarboxylated product was also present (Rt= 1.68 min). Saturated ammonium chloride (15 mL) was added to the crude reaction mixture and the mixture was transfrred to a separating funnel. Ethyl acetate (80 mL) was then added and the organic layer was separated (keeping the interfacial material with the organic layer). The aqueous layer was washed with ethyl acetate (2 x 80 mL portions). (Note: During this extraction, a solid, presumably the required product was seen to crash out in the organic layer. If this reaction is to be repeated a work-up free approach is recommended where the crude reaction mixture is dry-loaded directly onto silica for chromatographic purification). The solvent was removed from the combined organics under reduced pressure. The crude product was loaded onto a pre- wetted silica column using the minimum DCM and methanol. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% DCM (5% methanolic ammonia) in DCM. Pure fractions were evaporated to dryness to afford 744 mg of impure product. The crude residue was triturated with Et2O to give a solid which was collected by filtration and dried under vacuum to give ethyl 2-(4-chloropyridin-2-ylamino)oxazole-5-carboxylate (415 mg, 44.3 %) as a beige solid. Conclusion: The desired product was isolated in moderate yield and high purity (95% based on strength NMR). The moderate yield may be improved under a longer reaction time, it is also probable that purification difficulties were also detrimental to the yield of this reaction.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:CCOC(=O)C1=CN=C(O1)N, Reagents are:Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: To make the coupled product on a larger scale for hydrolysis/decarboxylation Pd2(dba)3 (80 mg, 0.09 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (152 mg, 0.26 mmol), 2,4-dichloropyridine (0.378 mL, 3.50 mmol), cesium carbonate (2279 mg, 6.99 mmol) and ethyl 2-aminooxazole-5-carboxylate (546 mg, 3.50 mmol) were added to an oven dried microwave vial and the vial was capped and placed under an inert atmosphere, dioxane (18 mL) was added and the resulting mixture was heated to 160 °C for 1 h by microwave irradiation under a nitrogen atmosphere. The crude product was purified by flash silica chromatography, elution gradient 0 to 3% MeOH (7 N ammonia) in DCM. Pure fractions were evaporated to dryness to afford ethyl 2-(4-chloropyridin-2-ylamino)oxazole-5-carboxylate (892 mg, 95 %) as a brown solid. Analysis of the product after chromatography showed that it was ~ 75% pure by proton NMR and LCMS, therefore the actual yield of the desired product is closer to 70%. Note: the reaction was carried out twice on the above scale.

Here is a chemical reaction formula: Reactants are:amine:CCOC(=O)C1=CN=C(O1)N;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Poisoning experiment to find out if 2-aminooxazole or the coupled product from reaction of 2-aminooxazole and 2,4-dichloropyridine are 'poisoning' the catalyst. Reaction (a): Control reaction under identical conditions to EN04881-40 (should produce similar yield) Reaction (b): As for control but spiked with 2 eq. of 2-aminooxazole with respect to catalyst, before dioxane was added (will produce decreased yield if 2-aminooxazole is a poison) Reaction (c): As for control but spiked with 1 eq. of N-(4-chloropyridin-2-yl)oxazol-2-amine, before dioxane was added (will produce decreased yield if N-(4-chloropyridin-2-yl)oxazol-2-amine is a poison) Pd2(dba)3 (22.89 mg, 0.025 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (43.4 mg, 0.075 mmol), 2,4-dichloropyridine (148 mg, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol),ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol) and 4,4'-di-tert- butylbiphenyl (26.6 mg, 0.10 mmol) were added to an oven dried microwave vial, the vial was capped and placed under an inert atmosphere. Dioxane (4 mL) was added and the resulting mixture was heated to 140 °C for 1 h by microwave irradiation under a nitrogen atmosphere. An isolated yield was obtained for reaction (a). Dichloromethane (10 mL) was added to the crude reaction mixture and the mixture was adsorbed onto silica. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in heptane. Pure fractions were evaporated to dryness to afford ethyl 2-(4-chloropyridin-2-ylamino)oxazole-5-carboxylate (111 mg, 41.5 %) as a white solid. Taking into account that the crude LCMS for reaction (A) corresponds to a ~ 42% isolated yield, the amount of product can be calculated for reactions (B) and (C) using the ratio between the t-Butyl biphenyl and the required product in the LCMS. The amount of required product produced in reaction (B) was 41% and for reaction (C) 45% product was produced. Conclusion: The above compounds do not poison the catalyst. Note: Significant amounts of what is assumed to be the regioisomeric 4-aminated product were also formed in these reactions. Major regioisomer formed in ~ 4:1 ratio.

Here is a chemical reaction formula: Reactants are:amine:CCOC(=O)C1=CN=C(O1)N;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: To find out if the regioisomeric ester is also a reaction substrate in this C-N bond forming reaction Pd2(dba)3 (22.89 mg, 0.025 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (43.4 mg, 0.075 mmol), 2,4-dichloropyridine (148 mg, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol),ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol) were added to an oven dried microwave vial, the vial was capped and placed under an inert atmosphere, dioxane (4 mL) was added and the resulting mixture was heated at 140 °C for 1 h by microwave irradiation under a nitrogen atmosphere. The crude product was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in heptane. Pure fractions were evaporated to dryness to afford ethyl 2-(4-chloropyridin-2-ylamino)oxazole-5-carboxylate (135 mg, 50.5 %) as a white solid. Conclusion: The desired product was isolated in > 50% isolated yield. The electron withdrawing ester group again has a positive effect on this reaction. More work needs to be carried out to probe the origin of this effect. NOESY confirmed expected regioisomer was formed (see sample details).

Here is a chemical reaction formula: Reactants are:amine:CCOC(=O)C1=CN=C(O1)N;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C(C)(C)C)C(C)(C)C)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Series of experiments to optimise yield of the above coupled product. Pd2(dba)3 (22.89 mg, 0.025 mmol), di-tert- butyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (42.4 mg, 0.10 mmol), 2,4-dichloropyridine (148 mg, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol),ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol) and 4,4'-di-tert- butylbiphenyl (60 mg, 0.23 mmol) were added to an oven dried microwave vial, the vial was capped and placed under an inert atmosphere, dioxane (4 mL) was added and the resulting mixture was heated at 160 °C for 1 h by microwave irradiation under a nitrogen atmosphere. Crude LCMS shows a complete switch in regioselectivity, with the other isomer becoming the major product in 26% yield based on internal standard (note: this is a rough estimate as the U.V absorbance may be significantly different for this regioisomer). The regioisomeric ratio is 2.8:1 and although the product was not formed in synthetically useful yields, it is an interesting result. Conclusion: Switch in regioselectivty with the change in ligand may be worth pursuing.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:CCOC(=O)C1=CN=C(O1)N, Reagents are:Solvent:C1COCCO1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=C(C=CC(=C2P(C(C)(C)C)C(C)(C)C)OC)OC)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Series of experiments to optimise yield of the above coupled product. Pd2(dba)3 (22.89 mg, 0.025 mmol), di-tert- butyl(2',4',6'-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine (48.4 mg, 0.10 mmol), 2,4-dichloropyridine (148 mg, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol),ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol) and 4,4'-di-tert-butylbiphenyl (60 mg, 0.23 mmol) were added to an oven dried microwave vial, the vial was capped and placed under an inert atmosphere, dioxane (4 mL) was added and the resulting mixture was heated at 160 °C for 1 h by microwave irradiation under a nitrogen atmosphere. Crude LCMS shows a switch in regioselectivity, with the other isomer becoming the major product in 25% yield based on internal standard (note: this is a rough estimate as the U.V absorbance may be significantly different to the other regioisomer). The regioisomeric ratio is 1.7:1 and although the product was not formed in synthetically useful yields, it is an interesting result. Conclusion: Switch in regioselectivty with the change in ligand may be worth pursuing, although greater selectivity was seen for this prduct in the preceeding reaction.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:CCOC(=O)C1=CN=C(O1)N, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=C(C=CC(=C2P(C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F)OC)OC)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Series of experiments to optimise yield of the above coupled product. Pd2(dba)3 (22.89 mg, 0.025 mmol), bis(3,5-bis(trifluoromethyl)phenyl)(2',4',6'-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine (80 mg, 0.10 mmol), 2,4-dichloropyridine (148 mg, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol),ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol) and 4,4'-di-tert-butylbiphenyl (60 mg, 0.23 mmol) were added to an oven dried microwave vial, the vial was capped and placed under an inert atmosphere, dioxane (4 mL) was added and the resulting mixture was heated at 160 °C for 1 h by microwave irradiation under a nitrogen atmosphere. Crude LCMS shows a switch in regioselectivity again with respect to the bidentate ligand Xantphos, with the other isomer becoming the major product in 28% yield based on internal standard (note: this is a rough estimate as the U.V absorbance may be significantly different to the other regioisomer). None of the other regioisomer observed. Conclusion: Switch in regioselectivty with the change in ligand may be worth pursuing, this reaction is _apparently_ completely selective for the 4-regioisomer. Note: Necessary to isolate product to confirm.

Here is a chemical reaction formula: Reactants are:amine:CCOC(=O)C1=CN=C(O1)N;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Isolate a larger quantity of product for hydrolysis/decarboxylation study Pd2(dba)3 (91 mg, 0.10 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (173 mg, 0.30 mmol), 2,4-dichloropyridine (591 mg, 4.00 mmol), cesium carbonate (2604 mg, 7.99 mmol) and ethyl 2-aminooxazole-5-carboxylate (624 mg, 4.00 mmol) were added to an oven dried microwave vial. The vial was capped and placed under an inert atmosphere, dioxane (16 mL) was added and the resulting mixture was heated at 160 °C for 1 h by microwave irradiation under a nitrogen atmosphere. This reaction was run in four portions, i.e. four identical microwave reactions were carried out on 1/4 of the above scale. The reactions were then combined and purified as a single sample. Purification by chromatography on silica using heptane:ethyl acetate as eluent, on alumina with heptane:ethyl acetate and via reverse phase on C18 silica failed. The crude product was purified by flash silica chromatography, elution gradient 0 to 3% Methanolic ammonia (7 M) in DCM. Pure fractions were evaporated to dryness to afford ethyl 2-(4-chloropyridin-2-ylamino)oxazole-5-carboxylate (534 mg, 49.9 %) as a pale yellow solid. Althought the LCMS looks good for the fractions combined for this sample, the proton NMR shows significant impurities to be present. Conclusion: Sufficient material isolated for hydrolysis/decarboxylation study.

Here is a chemical reaction formula: Reactants are:amine:CCOC(=O)C1=CN=C(O1)N;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=C(C=CC(=C2P(C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F)OC)OC)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Attempt to synthesise the 4-substituted product using jackiephos as ligand. To an oven-dried microwave vial was added ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol), 2,4-dichloropyridine (0.108 mL, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.87 mg, 0.02 mmol) and bis(3,5-bis(trifluoromethyl)phenyl)(2',4',6'-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine (80 mg, 0.10 mmol) and the vial was capped and purged with nitrogen. dioxane (4 mL) (degassed) was added and the reaction mixture was heated to 160 °C for 1 h under microwave irradiation. The reaction mixture was heated to 160°C for a further 3 h due to incomplete conversion. DCM (10 mL) was added to the crude reaction mixture together with silica (2 g). The solvent was then removed from the reaction mixture under reduced pressure. The resulting residue was then added tom a dry-load tube prior to chromatography. The crude product was purified by flash silica chromatography, elution gradient 0 to 2.5% methanolic ammonia (7 M) in DCM. The desired product (4-substitution) was isolated as a mixture with the 2-substituted product. The ratio of the 2-isomer to the 4-isomer is 2.4:1 for the mxture with no other fractions containing either isomer. Conclusion: The apparent higher selectivity for the 4-isomer is due to the overlap of the 2,4-dichloropyridine starting material with this isomer. Therefore this reaction actually forms the 2-isomer selectively and is not a very active catalyst for this transformation.

Here is a chemical reaction formula: Reactants are:amine:CCOC(=O)C1=CN=C(O1)N;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=CN=C(O1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Comparison of the reactivity of 2-aminooxazole and ester substituted 2-aminooxazole under identical reaction conditions. To an oven-dried round bottomed flask was added ethyl 2-aminooxazole-5-carboxylate (156 mg, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.87 mg, 0.02 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (43.4 mg, 0.07 mmol) and 2,4-dichloropyridine (0.108 mL, 1.00 mmol). A reflux condenser was fitted and the vessel was purged with nitrogen. dioxane (2 mL)/DMSO (2 mL) (degassed) was added and the reaction mixture was heated to 100 °C for 16 h. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7M NH3/MeOH and pure fractions were evaporated to dryness to afford the crude product. The crude product was purified by flash silica chromatography, elution gradient 1 to 3% methanolic ammonia (7 M) in DCM. Pure fractions were evaporated to dryness to afford ethyl 2-(4-chloropyridin-2-ylamino)oxazole-5-carboxylate (128 mg, 47.9 %) as a pale yellow solid. Conclusion: The desired product was formed in moderate yield. Normal-phase column DCM:methanolic ammonia

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:C1=COC(=N1)N, Reagents are:Base:C(=O)([O-])[O-].[K+].[K+];Solvent:COC1=CC=CC=C1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:C1=CN=C(C=C1Cl)NC2=NC=CO2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Repeat of optimised conditions found in process research and devellopment screen for an isolated yield. An activated catalyst solution was prepared by adding TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (61.3 mg, 0.07 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (77 mg, 0.13 mmol) to an oven-dried microwave vial. The vial was then capped and purged with nitrogen and anisole (1 mL) (degassed) was added. The solution was stirred at 50°C for 40 mins, then 90°C for 15 mins (activated catalyst solution; Soln. 1). To another oven-dried microwave vial was added potassium carbonate (126 mg, 0.91 mmol), oxazol-2-amine (102 mg, 1.22 mmol) and 2,4-dichloropyridine (90 mg, 0.61 mmol) and the vial was capped and purged with nitrogen. anisole (1.35 mL) and the activated catalyst solution (0.45 mL of Soln. 1 from above) were then added (this corresponds to a catalyst loading of 10% Pd). The vessel was then heated to 120 °C for 16 h. LCMS of the crude reaction mixture indicated that the desired product was present (Rt= 1.70) along with a trace amount of the double addition product i.e. amine addition at the 2- and 4-position (Rt= 1.22 min). The reaction mixture was quenched with saturated ammonium chloride (8 mL) and transferred to a separating funnel. Ethyl acetate (15 mL) was then added and the organic layer was separated (keeping the interfacial material with the organic layer). The aqueous layer was washed with ethyl acetate (2 x 15 mL portions). The combined organics were then dried over sodium sulfate, filtered and the solvent was removed under reduced pressure. DCM (1 mL) was then added to the resulting residue (which still contained anisole (4 mL)) and this solution was loaded directly onto a silica column (40 g). The crude product was purified by flash silica chromatography, elution gradient 0 to 30% DCM (5% methanolic ammonia) in DCM, then 100% DCM (5% methanolic ammonia). Pure fractions were evaporated to dryness to afford N-(4-chloropyridin-2-yl)oxazol-2-amine (59.0 mg, 49.6 %) as an off-white solid. Note: This product was only 52% pure based on NMR strength. Conclusion: The desired product was isolated but in relatively low yield and low purity.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:C1=COC(=N1)N, Reagents are:metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=C(C=CC(=C2P(C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F)OC)OC)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1, and Products are 0:C1=CN=C(C=C1Cl)NC2=NC=CO2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Reactions using ligands not previously tested under these conditions 2,4-dichloropyridine (0.109 mL, 1.01 mmol), oxazol-2-amine (85 mg, 1.01 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (23.20 mg, 0.03 mmol), bis(3,5-bis(trifluoromethyl)phenyl)(2',4',6'-triisopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine (81 mg, 0.10 mmol) and cesium carbonate (660 mg, 2.03 mmol) were added to an oven-dried microwave vail and the vial was purged with nitrogen. Degassed dioxane (4mL) was then added and the reaction mixture was heated to 140 °C for 1 h under microwave irradiation. Conclusion: None of the desired product was observed in the LCMS of the crude reaction mixture, not progressed.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:C1=COC(=N1)N, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1, and Products are 0:C1=CN=C(C=C1Cl)NC2=NC=CO2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: To isolate some of the required product to provide an analytical sample for a large catalyst screen. 2,4-dichloropyridine (0.109 mL, 1.01 mmol), oxazol-2-amine (85 mg, 1.01 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.89 mg, 0.02 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (44.0 mg, 0.08 mmol) (Xantphos) and cesium carbonate (660 mg, 2.03 mmol) were added to a microwave vail and the vial was purged with nitrogen. Degassed dioxane (4 mL) was then added and the reaction mixture was heated to 140 °C for 1 h under microwave irradiation. LCMS of crude reaction mixture showed some of the required product was formed, however the LCMS using acidic modifier was somewhat misleading as a side- product co-elutes with the required product thus giving the impression that a greater amount of product was formed than is the case. LCMS under acidic modifier is more informative. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% heptane in EtOAc. Pure fractions were evaporated to dryness to afford N-(4-chloropyridin-2-yl)oxazol-2-amine (4.00 mg, 2.018 %) as a pale yellow residue. Conclusion: 4 mg of impure product was isolated.

Here is a chemical reaction formula: Reactants are:amine:C1=COC(=N1)N;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:Solvent:C1COCCO1;Base:[H-].[Na+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:C1=CN=C(C=C1Cl)NC2=NC=CO2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: If deprotonation is rate-determining in this coupling quantitative deprotonation prior to subjection to coupling conditions should prove beneficial. To an oven dried microwave vial was added oxazol-2-amine (85 mg, 1.01 mmol) together with sodium hydride (40.5 mg, 1.01 mmol), the vial was capped and purged with nitrogen and dioxane (1 mL) was added. The mixture was then stirred at rt for 1 h (initially effervescence was observed but subsided within 20 min of stirring). To the above vial was added 2,4-dichloropyridine (0.109 mL, 1.01 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (22.89 mg, 0.02 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (44.0 mg, 0.08 mmol) (Xantphos) as a solution in dioxane (2 mL) and the reaction mixture was heated to 140 °C for 1 h under microwave irradiation. Dichloromethane (10 mL) was added to the crude reaction mixture and the mixture was absorbed onto silica. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in heptane. Pure fractions were evaporated to dryness to afford N-(4-chloropyridin-2-yl)oxazol-2-amine (6.00 mg, 3.03 %) as a pale yellow dry film. Conclusion: The formal deprotonation appears to have had no benificial effect on this coupling.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:C1=COC(=N1)N, Reagents are:Base:[O-]P(=O)([O-])[O-].[K+].[K+].[K+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1, and Products are 0:C1=CN=C(C=C1Cl)NC2=NC=CO2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Objective: Will increased catalyst loading lead to increased isolated yield of the desired product? 2,4-dichloropyridine (0.109 mL, 1.01 mmol), oxazol-2-amine (102 mg, 1.22 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (186 mg, 0.20 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (352 mg, 0.61 mmol) (Xantphos) and potassium phosphate (430 mg, 2.03 mmol) were added to a microwave vail and the vial was purged with nitrogen. Degassed dioxane (4mL) was then added and the reaction mixture was heated to 160 °C for 6 h under microwave irradiation. Dichloromethane (10 mL) was added to the crude reaction mixture and the mixture was adsorbed onto silica gel. The crude product was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in heptane. Unfortunately and somewhat surprisingly, none of the desired product was isolated, although only a trace of required product was observed in the LCMS of the crude reaction mixture. Conclusion: It appears that under this higher catalyst loading the reaction is less efficent, potentially a concentration effect?

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:C1=COC(=N1)N, Reagents are:metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+], and Products are 0:C1=CN=C(C=C1Cl)NC2=NC=CO2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To a vial containing oxazol-2-amine (102 mg, 1.22 mmol), , TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (9.28 mg, 10.14 µmol), 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (9.47 mg, 0.02 mmol) and sodium 2-methylpropan-2-olate (136 mg, 1.42 mmol), was added degassed toluene (4 mL) and 2,4-dichloropyridine (0.109 ml, 1.01 mmol) and the reaction mixture was heated to 100 degrees C for 20 h. None of the desired product was observed by LCMS or in crude proton NMR. **It is of note that although the 2,4-dichloropyridine is present in the crude proton NMR, the oxazole-2-amine is not**. It is possible that under the strongly basic reaction conditions that this starting material decomposed. Product not isolated.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:C1=COC(=N1)N, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1;Base:C1=CC=C(C=C1)[O-].[Na+], and Products are 0:C1=CN=C(C=C1Cl)NC2=NC=CO2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To a microwave vial containing 2,4-dichloropyridine (0.109 mL, 1.01 mmol), sodium phenolate (177 mg, 1.52 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (11.60 mg, 0.01 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (17.59 mg, 0.03 mmol) (Xantphos), was added degassed dioxane (4 mL) and the mixture allowed to stir under nitrogen atmosphere for 5 min. To this solution was added oxazol-2-amine (94 mg, 1.11 mmol) and the reaction mixture was heated to 130 °C for 30 min under microwave irradiation. **Apparently no 2-aminooxazole remains by proton NMR of crude reaction mixture upon removal of dioxane, however it's presence was observed by LCMS of the crude reaction mixture (see attached). It is possible that the presence of impurities/solvent etc. have shifted the resonances slightly for this starting material in** **1** **H NMR.** The crude product was purified by reverse-phase flash chromatography on C-18 modified silica, elution gradient 0 to 100% MeCN in water. Pure fractions were evaporated to dryness to afford N-(4-chloropyridin-2-yl)oxazol-2-amine (6.00 mg, 3.03 %) as a pale yellow dry film. 3 % of the required product was isolated and this sample was impure. Microwave heating has no positive effect under these reaction conditions. Upon submission of a crude sample of the reaction mixture to both starting materials were observed. Conclusion: 3% of impure material isolated, look for alternative conditions.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:C1=COC(=N1)N, Reagents are:Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:C1=CN=C(C=C1Cl)NC2=NC=CO2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Palladium(II) acetate (11.38 mg, 0.05 mmol) was added in a single portion to a degassed solution of 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (44.0 mg, 0.08 mmol), oxazol-2-amine (85 mg, 1.01 mmol), cesium carbonate (768 mg, 2.36 mmol),2,4-dichloropyridine (0.109 mL, 1.01 mmol), dioxane (4 mL) and DMSO (0.8 mL) and the resulting mixture was heated at 100 °C for 16 hours under a nitrogen atmosphere. Note: the reaction mixture was degassed by first combing the reagents (with the exception of Pd((OAc)2), sealing the vessel and carrying out three pump- purge cycles (vac-nitrogen). Dioxane was then added to this mixture via syringe, followed by the Pd(OAc)2 in a single portion and the vessel was heated for the required time as above. Solvent boiled dry from reaction overnight. Only DMSO remained. **Crude proton NMR shows mainly dichlorpyridine starting material and the 2-aminooxazole starting material was absent**. Crude LCMS indicates that a product of the required mass is present. The crude product was purified by flash chromatography on C-18 modified silica, elution gradient 0 to 100% MeCN in water with basic modifier (1% ammonium hydroxide). Pure fractions were evaporated to dryness to afford N-(4-chloropyridin-2-yl)oxazol-2-amine (22.00 mg, 11.10 %) as a pale yellow residue. The product isolated, although impure, looks like the required product based on LCMS. The 1H NMR of the purified material is in D6-DMSO here and so not directly comparable with previous spectra in CDCl3. Conclusion: This may be worth pursuing (i.e. adding DMSO to aid solubility) based on the slightly increased yield. **Revision: Required product not isolated, spectral analysis of isolated sample does not match those of authentic samples of the coupled product** .

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CN=C(C=C1Cl)Cl;amine:C1=COC(=N1)N, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:CC(=O)N(C)C, and Products are 0:C1=CN=C(C=C1Cl)NC2=NC=CO2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: oxazol-2-amine (85 mg, 1.01 mmol), 2,4-dichloropyridine (0.151 mL, 1.01 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (70.4 mg, 0.12 mmol) and cesium carbonate (660 mg, 2.03 mmol) were stirred in DMA (5 mL). The mixture was purged with nitrogen for 10 minutes. Palladium(II) acetate (22.76 mg, 0.10 mmol) was added and the mixture heated at 100 °C for 70h. The mixture was cooled, filtered and concentrated. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 19 mm diameter, 100 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford N-(4-chloropyridin-2-yl)oxazol-2-amine (3.90 mg, 1.967 %).

Here is a chemical reaction formula: Reactants are:amine:C1=COC(=N1)N;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:C1=CC=C(C=C1)[O-].[Na+], and Products are 0:C1=CN=C(C=C1Cl)NC2=NC=CO2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To a flask containing 2,4-dichloropyridine (0.109 mL, 1.01 mmol), sodium phenolate (177 mg, 1.52 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (11.60 mg, 0.01 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (17.59 mg, 0.03 mmol) (Xantphos), was added degassed dioxane (4 mL) and the mixture allowed to stir under nitrogen atmosphere for 5 min. To this solution was added oxazol-2-amine (94 mg, 1.11 mmol) and the reaction mixture was heated to 80 °C for three hours. A 1H NMR was measured of the crude reaction after the solvent had been removed. **This indicated the presence of significant amounts of 2,4-dichloropyridine as well as 2-amino oxazole**. LCMS of the crude reaction mixture at t= 90 min and at t= 3 h showed the desired product was present. The crude reaction mixture was dry loaded without workup and purified by automated flash chromatography.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC(=CC(=C1)OC(F)(F)F)C2=CN=C3N2N=C(C=C3)Cl;amine:CN1CCC(CC1)CN, Reagents are:metal and ligand:CN(C)C1=CC=CC=C1C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:CC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1, and Products are 0:CN1CCC(CC1)CNC2=NN3C(=NC=C3C4=CC(=CC=C4)OC(F)(F)F)C=C2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A 300 ml round bottom lfask was charged with a magnetic stir bar, toluene (39 ml), 6-chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine (1.1 g, 3.51 mmol), Pd2(dba)3 (0.321 g, 0.35 mmol), 2-(DIMETHYLAMINO)-2'-(DICYCLOHEXYLPHOSPHINO)BIPHENYL (0.414 g, 1.05 mmol), SODIUM TERT-BUTOXIDE (1.011 g, 10.52 mmol), and (1-methylpiperidin-4-yl)methanamine (0.674 g, 5.26 mmol). The mixture was degassed with N2, the vessel fitted with a reflux condenser, and then placed in an oil bath heated to 110 °C for 16hrs. The mixture was cooled to r.t, filtered throught a bed of celite, washed with methanol, the filtrate was concentrated, the residue was pre-absorbed onto silca gel (~10g) and purified with ISCO (eluent methanol/DCM (1/3) to afford the title compound N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine (0.510 g, 35.9 %). (Note: the ligand I used was old) (note: tried direct displacement under microwave radiation at 180°C in 4MHCl or KOtBu in methoxyethanol; both condition didn't result in the desired product).

Here is a chemical reaction formula: Reactants are:amine:CN1CCC(CC1)CN;aryl halide:C1=CC(=CC(=C1)OC(F)(F)F)C2=CN=C3N2N=C(C=C3)Cl, Reagents are:Base:CC(C)(C)[O-].[Na+];metal and ligand:CN(C)C1=CC=CC=C1C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:CC1=CC=CC=C1, and Products are 0:CN1CCC(CC1)CNC2=NN3C(=NC=C3C4=CC(=CC=C4)OC(F)(F)F)C=C2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A 500 ml round bottom lfask was charged with a magnetic stir bar, toluene (200 ml), 6-chloro-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazine (6.55 g, 20.88 mmol), Pd2dba3 (1.912 g, 2.09 mmol), fresh bottle of 2'-(dicyclohexylphosphino)-N,N-dimethylbiphenyl-2-amine (2.465 g, 6.26 mmol), SODIUM TERT-BUTOXIDE (8.03 g, 83.53 mmol) and (1-methylpiperidin-4-yl)methanamine (4.55 g, 35.50 mmol). The mixture was degassed with N2, the vessel fitted with a reflux condenser, and then placed in an oil bath heated to 120 °C for 16hrs. The mixture was filtered throught a bed of celite, washed with methanol/DCM (3/1), the filtrate was concentrated, the residue was taken into a mixture of water and DCM/Isopropanol (5/1), separated, the water layer was extrated twice with DCM/isopropanol (5/1), the combined organics were dried (MgSO4), concentrated, the residue was pre- absorbed onto silca gel (~80g) and purified with ISCO (eluent methanol/DCM (1/3) to afford the title compound as which was taken into hexane, the solid was collected by filtration, washed with hexane, dried in vacum at 60°C to yield a light yellow solid as N-((1-methylpiperidin-4-yl)methyl)-3-(3-(trifluoromethoxy)phenyl)imidazo[1,2-b]pyridazin-6-amine (5.51 g, 62.9 %). 405mgs of the free base product was dissolved into 2ml of methanol, treated with 1M H2SO4 in methanol (1ml conc. H2SO4 + 17ml of methanol). The solution was stirred for 2min, solid crushed out, the suspension was continually stirred at r.t for overnight before being diluted with ethyl ether, the solid was collected by filtration, dried to yield a white solid as desired product- bi-sulfuric acid.

Here is a chemical reaction formula: Reactants are:amine:CC1=NC2=C(C=C1)C=C(C=C2)C(=O)N;aryl halide:CC1=C(C=C(C=C1)[N+](=O)[O-])Br, Reagents are:metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CC1=C(C=C(C=C1)[N+](=O)[O-])NC(=O)C2=CC3=C(C=C2)N=C(C=C3)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM(0) (9.10 mg, 9.94 µmol) was added to 2-bromo-1-methyl-4-nitrobenzene (42.9 mg, 0.20 mmol), 2-methylquinoline-6-carboxamide (37.0 mg, 0.20 mmol), cesium carbonate (194 mg, 0.60 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (11.50 mg, 0.02 mmol) in dioxane (2 mL) at 20°C under nitrogen. The resulting solution was stirred at 100 °C for 6 hours. Reaction seen to be progressing but very sluggish (5% conversion). Reaction abandoned.

Here is a chemical reaction formula: Reactants are:aryl halide:C1CC1NC2=CC(=NC3=C(C=NN23)C#N)Cl;amine:CC(=O)NC1=C(C=CC(=C1)N)N2CC[C@H](C2)NC(=O)OC(C)(C)C, Reagents are:Solvent:CN1CCCC1=O;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C(C)(C)C)C(C)(C)C)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CC(=O)NC1=C(C=CC(=C1)NC2=NC3=C(C=NN3C(=C2)NC4CC4)C#N)N5CC[C@H](C5)N, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (300 mg, 1.28 mmol), (R)-tert-butyl 1-(2-acetamido-4-aminophenyl)pyrrolidin-3-ylcarbamate (429 mg, 1.28 mmol), CESIUM CARBONATE (837 mg, 2.57 mmol) and di-tert- butyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (54.5 mg, 0.13 mmol) were added into NMP (6 mL) in a 50mL round bottle. Pd2dba3 (58.8 mg, 0.06 mmol) was added to the solution. The solution was purged by nitrogen, then heated at 105°C overnight. Crude product was separarted between water and ethyl acetate. The organic layer was concentrated under reduced pressure. The crude product was purified on the ISCO(17g silica column, EA/hex 0-75%). Then the intermediate was put in 1N HCl in ether(5mL),. The solution was stirred at rt for2hrs. Crude product was purified on Gilson(0.1%TFA CH3CN/water 2-35%), 124.8mg final product was obtained as white solid

Here is a chemical reaction formula: Reactants are:aryl halide:CCOC(=O)C1=CC2=C(O1)C=CC=C2Br;amine:CC(C)(C)OC(=O)N1CCNCC1, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=CC2=C(C=CC=C2O1)N3CCN(CC3)C(=O)OC(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: tert-butyl piperazine-1-carboxylate (0.692 g, 3.72 mmol), ethyl 4-bromobenzofuran-2-carboxylate (1 g, 3.72 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (0.177 g, 0.37 mmol), Tris(dibenzylideneacetone)dipalladium(0) (0.170 g, 0.19 mmol) and CESIUM CARBONATE (1.574 g, 4.83 mmol) were heated under argon to 95 °C overnight. The mixture was allowed to cool. The mixture was diluted with EtOAc and the mixture was filtered through a pad of Celite. The filterate was collected and the solvent was removed by rotary evaporation. The crude product was added to a silica gel column and was eluted with 0-50% EtOAc in heptane. The collected fractions were combined and the solvent was removed to yield tert-butyl 4-(2-(ethoxycarbonyl)benzofuran-4-yl)piperazine-1-carboxylate (0.990 g, 71.1 %). 1H NMR in CDCl3 is consistent with desired product MS (m+1) = 375.6. HPLC Peak RT = 3.27 minutes is product. Purity = 95%.

Here is a chemical reaction formula: Reactants are:amine:CC(C)(C)OC(=O)N1CCNCC1;aryl halide:CCOC(=O)C1=CC2=C(O1)C=CC=C2Br, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=CC2=C(C=CC=C2O1)N3CCN(CC3)C(=O)OC(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: ethyl 4-bromobenzofuran-2-carboxylate (7.7 g, 28.61 mmol), tert-butyl piperazine-1-carboxylate (5.33 g, 28.61 mmol), Tris(dibenzylideneacetone)dipalladium(0) (1.310 g, 1.43 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (1.364 g, 2.86 mmol) and CESIUM CARBONATE (12.12 g, 37.20 mmol) in dioxane (40 mL) was heated under argon to 95 °C overnight. The mixture was allowed to cool. The mixture was diluted with EtOAc and the mixture was filtered through a pad of Celite. The filterate was collected and the solvent was removed by rotary evaporation. The crude product was added to a silica gel column and was eluted with 0-50% EtOAc in heptane. The collected fractions were combined and the solvent was removed to yield tert-butyl 4-(2-(ethoxycarbonyl)benzofuran-4-yl)piperazine-1-carboxylate (4.92 g, 45.9 %). MS (m+1) = 375.8. HPLC Peak RT = 3.27 minutes is product. Purity = 96%.

Here is a chemical reaction formula: Reactants are:amine:CC(C)(C)OC(=O)N1CCNCC1;aryl halide:CCOC(=O)C1=CC2=C(O1)C=CC=C2Br, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC(C)C1=CC(=C(C(=C1)C(C)C)C2=CC=CC=C2P(C3CCCCC3)C4CCCCC4)C(C)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=CC2=C(C=CC=C2O1)N3CCN(CC3)C(=O)OC(C)(C)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: ethyl 4-bromobenzofuran-2-carboxylate (2 g, 7.43 mmol), tert-butyl piperazine-1-carboxylate (1.384 g, 7.43 mmol), Tris(dibenzylideneacetone)dipalladium(0) (0.340 g, 0.37 mmol), 2-Dicyclohexylphosphino-2',4',6'-tri-iso-propyl-1,1'-biphenyl (0.354 g, 0.74 mmol) and CESIUM CARBONATE (3.15 g, 9.66 mmol) were heated under argon to 95 °C overnight. The mixture was allowed to cool. The mixture was diluted with EtOAc and the mixture was filtered through a pad of Celite. The filterate was collected and the solvent was removed by rotary evaporation. The crude product was added to a silica gel column and was eluted with 0-50% EtOAc in heptane. The collected fractions were combined and the solvent was removed to yield tert-butyl 4-(2-(ethoxycarbonyl)benzofuran-4-yl)piperazine-1-carboxylate (1.250 g, 44.9 %). MS (m+1) = 375.6. HPLC Peak RT = 3.29 minutes is product. Purity = 99%.

Here is a chemical reaction formula: Reactants are:aryl halide:CN1CC(OC2=C(C1)C=CC(=N2)Cl)CC(F)(F)F;amine:CN1C=C(C=CC1=O)C2=C(N=C(C=C2)N)OC, Reagents are:Base:CCC(C)(C)[O-].[Na+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN1CC(OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(C(=O)C=C4)C)OC)CC(F)(F)F, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A mixture of 5-(6-amino-2-methoxypyridin-3-yl)-1-methylpyridin-2(1H)-one (0.2 g, 0.86 mmol), 8-chloro-4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.243 g, 0.86 mmol), Palladium(II) acetate (0.019 g, 0.09 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (0.050 g, 0.09 mmol) and Sodium tert-pentoxide (0.114 g, 1.04 mmol) in dioxane (1.5 mL) was heated by microwave irradiation to 120 °C for 30 min. The mixture was allowed to cool. DCM (5 mL) was added and the mixture was filtered through a short pad of Celite. The filtrate was collected and the solvent was removed by rotary evaporation. The crude product was added to a silica gel column and was eluted with 0-5% MeOH in DCM. The collected fractions were combined and the solvent was removed by rotary evaporation. The residue was submitted for separation by chiral SFC to yield 5-(2-methoxy-6-(4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-ylamino)pyridin-3-yl)-1-methylpyridin-2(1H)-one (0.055 g, 26.8 %) and 5-(2-methoxy-6-(4-methyl-2-(2,2,2-trifluoroethyl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepin-8-ylamino)pyridin-3-yl)-1-methylpyridin-2(1H)-one (0.051 g, 24.80 %). EN04155-91-001: 1H NMR in DMSO-d6 is consistent with desired product MS (m+1) = 476.1. HPLC Peak RT = 2.48 minutes is product. Purity = 97%. EN04155-91-002: 1H NMR in DMSO-d6 is consistent with desired product MS (m+1) = 476.1. HPLC Peak RT = 2.48 minutes is product. Purity = 98%.

Here is a chemical reaction formula: Reactants are:amine:COC(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=C(C=C(C=C1F)Br)F, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC1(C2=C(C(=CC=C2)[PH+](C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5[PH+](C6=CC=CC=C6)C7=CC=CC=C7)C.C1=[C-]C=C(C=C1F)F.Br[Pd+], and Products are 0:COC(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC(=C4)F)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Pd complexe (147 mg, 0.17 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (600 mg, 1.67 mmol), 1-bromo-3,5-difluorobenzene (0.241 ml, 2.09 mmol) and cesium carbonate (818 mg, 2.51 mmol) dissolved in 1,4-dioxane (12 ml). The resulting suspension was degased with argon and then stirred at 100 °C (15:00) for 18 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was adsorbed on silica gel and purified by flash chromatography on silica gel eluting with 0 to 6% methanol in ethyl acetate. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (314 mg, 39.9 %) as a clear yellow solid. **low yield but LCMS of the crude showed a nice reaction!** LCMS is OK.

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=C(C=C1F)Br)F;amine:COC(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC1(C2=C(C(=CC=C2)[PH+](C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5[PH+](C6=CC=CC=C6)C7=CC=CC=C7)C.C1=[C-]C=C(C=C1F)F.Br[Pd+], and Products are 0:COC(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC(=C4)F)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Pd complexe (33.2 mg, 0.04 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (270 mg, 0.75 mmol), 1-bromo-3,5-difluorobenzene (0.095 ml, 0.83 mmol) and cesium carbonate (368 mg, 1.13 mmol) dissolved in 1,4-dioxane (5 ml). The resulting suspension was degased with argon and then stirred at 80 °C. After 18 hours, lcms showed incomplete reaction: 5% more reactants were added and heating was continued at 100 °C for 5 additionnal hours. Lcms showed ~ complete reaction after 23 hours. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 6% methanol in ethyl acetate. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (206 mg, 58.1 %) as a clear yellow foam. LCMS and NMR are OK

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=C(C=C1F)Br)F;amine:COC(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC1(C2=C(C(=CC=C2)[PH+](C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5[PH+](C6=CC=CC=C6)C7=CC=CC=C7)C.C1=[C-]C=C(C=C1F)F.Br[Pd+], and Products are 0:COC(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC(=C4)F)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Pd complexe (142 mg, 0.16 mmol) was added to a stirred mixture of methyl 2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxylate (577 mg, 1.61 mmol), 1-bromo-3,5-difluorobenzene (0.232 ml, 2.01 mmol) and cesium carbonate (787 mg, 2.41 mmol) dissolved in 1,4-dioxane (12 ml). The resulting suspension was degased with argon and then stirred at 100 °C (10:30). After 3 hours, lcms showed complete reaction. The reaction mixture was allowed to cool to room temperature, filtered and concentrated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 6% methanol in ethyl acetate. The solvent was evaporated to dryness to afford methyl 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-2-morpholino-4-oxo-4H-chromene-6-carboxylate (315 mg, 41.6 %) as a clear yellow foam. **low yield but LCMS of the crude showed complete reaction!** LCMS and NMR are OK

Here is a chemical reaction formula: Reactants are:amine:CCOC(=O)C1=COC(=N1)N;aryl halide:C1=CN=C(C=C1Cl)Cl, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CCOC(=O)C1=COC(=N1)NC2=NC=CC(=C2)Cl, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Pd2(dba)3 (22.89 mg, 0.025 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (43.4 mg, 0.075 mmol), 2,4-dichloropyridine (148 mg, 1.00 mmol), cesium carbonate (651 mg, 2.00 mmol),ethyl 2-aminooxazole-4-carboxylate (156 mg, 1.00 mmol) were added to an oven dried microwave vial, the vial was capped and placed under an inert atmosphere, dioxane (4 mL) was added and the resulting mixture was heated to 140 °C for 1 h by microwave irradiation under a nitrogen atmosphere. The crude product was purified by reverse-phase flash chromatography, elution gradient 0 to 100% MeCN in water. Pure fractions were evaporated to dryness to afford ethyl 2-(4-chloropyridin-2-ylamino)oxazole-4-carboxylate (99 mg, 37.0 %) as a pale yellow solid. Conclusion: Yield produced under microwave conditions is essentially identical to overnight reaction with conventional heating. Therefore screening of other aminooxazoles can be carried out under microwave conditions in the interest of time. .

Here is a chemical reaction formula: Reactants are:aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3;amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, Reagents are:metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[K+].[K+], and Products are 0:CN1C[C@H](OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5=CC=CC=C5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Charged a standard microwave vial with a mixture of 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (0.500 g, 2.45 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (0.611 g, 2.22 mmol), palladium (II) acetate (0.015 g, 0.07 mmol), rac-BINAP (0.069 g, 0.11 mmol), potassium carbonate (0.461 g, 3.34 mmol), and toluene (20 mL). The atmosphere was inerted through consecutive vacuum-nitrogen purge cycles, then heated at 120 °C for 16 hours. HPLC-UV shows some starting materials remaining (<11% at 254 nm). The mixture was cooled to room temperature and 20 mL of DCM was added to the vessel. The pH was adjusted to pH 2 with 2.0N aqueous HCl and the phases were separated. Basified the aqueous with 2.0 M aqueous NaOH and extracted with 2 X 30 mL DCM. The organics were combined, dried with magnesium sulfate and concentrated by rotary evaporator to yield EN04092-36-001 (811 mg, 1.833 mmol, 82 %).

Here is a chemical reaction formula: Reactants are:aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3;amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, Reagents are:metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+], and Products are 0:CN1C[C@H](OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5=CC=CC=C5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (528 mg, 2.58 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (710 mg, 2.58 mmol), Sodium tert-butoxide (373 mg, 3.88 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (113 mg, 0.18 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (166 mg, 0.18 mmol) were added to a microwave vial followed by toluene (10.5 mL). The reaction mixture was flushed with nitrogen and the mixture was heated to 100°C and stirred overnight. The reaction was complete. The solids were filtered off and washed with ethyl acetate. The organic solution was extracted by sat NaHCO3 solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography using DCM : [DCM:MeOH:NH3=90:10:1] = 100:0 to 60:40 as gradient. The product was obtained as yellow foam 766 mg purity 95-99% depending on wavelength (95% on 220nm). The compound was dissolved in DCM and treated with activated carbon, then filtered and concentrated. The purity was **not** increased by the treatment! Preparative purification with Gilson prep was performed, 30-70% gradient was used. The material was collected manually. The fractions were pooled together, concentrated in vacuo then treated with DCM and sat NaHCO3 solution. The phases were separated, the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The product was obtained as white foam and was dried overnight in a vacuum oven at 40°C.

Here is a chemical reaction formula: Reactants are:amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC;aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3, Reagents are:Base:C(=O)([O-])[O-].[K+].[K+];Solvent:CC1=CC=CC=C1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN1C[C@H](OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5=CC=CC=C5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Charged a round-bottom flask with a mixture of 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (5.0 g, 24.48 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (6.73 g, 24.48 mmol), palladium (II) acetate (0.165 g, 0.73 mmol), rac-BINAP (0.762 g, 1.22 mmol), potassium carbonate (5.08 g, 36.72 mmol), and toluene (100 mL). The atmosphere was inerted through consecutive vacuum-nitrogen purge cycles, then heated at 120 °C for 16 hours. HPLC-UV shows a small percentage (<5%) of starting materials remaining. Heating was continued for another 2 hours, then the heating block was removed and the mixture was allowed to cool to room temperature. Added 200 mL dichloromethane and adjusted the pH to 2 with 2.0N aqueous HCl. Separated the phases and basified the aqueous with 1.0N aqueous sodium hydroxide. Extracted with 200 mL DCM, followed by a second extraction with 100 mL DCM. The organics were dried with magnesium sulfate and concentrated by rotary evaporator to yield EN04092-37-001 (10.9 g, 24.63 mmol, 101 %) as an amber-coloured foam.

Here is a chemical reaction formula: Reactants are:aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3;amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, Reagents are:Base:C(=O)([O-])[O-].[K+].[K+];Solvent:CC1=CC=CC=C1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN1C[C@H](OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5=CC=CC=C5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Charged a round-bottom flask with a mixture of 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (7.6 g, 37.21 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (10.22 g, 37.21 mmol), palladium (II) acetate (0.251 g, 1.12 mmol), rac-BINAP (1.159 g, 1.86 mmol), potassium carbonate (7.71 g, 55.82 mmol), and toluene (150 mL). The atmosphere was inerted through consecutive vacuum-nitrogen purge cycles, then heated at 120 °C for 16 hours. HPLC-UV shows <9% of starting materials remaining. Added an additional 25mg palladium acetate and 116 mg BINAP, then heating was continued for another 2 hours. HPLC-UV does not show any additional progress. The heating block was removed and the mixture was allowed to cool to room temperature. Added 300 mL dichloromethane and adjusted the pH to 2 with 2.0N aqueous HCl. Separated the phases and basified the aqueous with 1.0N aqueous sodium hydroxide. Extracted with 200 mL DCM, followed by a second extraction with 100 mL DCM. The organics were dried with magnesium sulfate and concentrated by rotary evaporator to yield EN04092-38-001 (16.1 g, 36.4 mmol, 98 %) as an amber-coloured foam.

Here is a chemical reaction formula: Reactants are:aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3;amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, Reagents are:Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[K+].[K+];metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN1C[C@H](OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5=CC=CC=C5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Charged a round-bottom flask with a mixture of 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (4.5 g, 22.03 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (6.05 g, 22.03 mmol), palladium (II) acetate (0.148 g, 0.66 mmol), rac-BINAP (0.686 g, 1.10 mmol), potassium carbonate (4.57 g, 33.05 mmol), and toluene (90 mL). The atmosphere s inerted through itrogen purge cycles, then heated at 120 °C or 16 hours. HPLC-UV shows <5% of starting materials remaining. The heating block was removed and the mixture was allowed to cool to room temperature. Added 300 mL dichloromethane and adjusted the pH to 2 with 2.0N aqueous HCl. Separated the phases and basified the aqueous with 1.0N aqueous sodium hydroxide. Extracted with 200 mL DCM, followed by a second extraction with 100 mL DCM. The organics were dried with magnesium sulfate and concentrated by rotary evaporator to give EN04092-39-001 (9.90g, 22.37 mmol, 102%) name='[Samples]' index='0' field='Samples' type='field' length='9'/>ber- coloured foam.

Here is a chemical reaction formula: Reactants are:aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3;amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, Reagents are:Base:CC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:CN1C[C@H](OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5=CC=CC=C5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (0.892 g, 4.37 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (1.20 g, 4.37 mmol), Sodium tert-butoxide (0.630 g, 6.55 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.272 g, 0.44 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (0.200 g, 0.22 mmol) were added to a microwave vial followed by toluene (16 mL). The reaction mixture was flushed with nitrogen and the mixture was heated to 100°C and stirred overnight. The reaction was completed. The solids were filtered off and washed with DCM. The organic solution was extracted by sat NaHCO3 solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography using DCM : [DCM:MeOH:NH3=90:10:1] = 100:0 to 60:40 as gradient. The product was obtained as yellow foam 1.55 g with a purity 96-99% depending on wavelength (96% on 220nm). Preparative purification with Gilson prep was performed, 30-70% gradient was used. The material was collected manually. The fractions were pooled together, concentrated in vacuo then treated with DCM and sat NaHCO3 solution. The phases were separated. The aqueous layer was extracted with DCM 2 more times than once with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The product was obtained as white foam and was dried overnight in a vacuum oven at 50°C. According to 1H-NMR 1.5 % ethyl acetate was present in the sample. **Ethyl acetate should be avoided for extraction!** The sample was dissolved in DCM and concentrated in vacuo then the process was repeated 2 more times. The product was dried in a vacuum oven overnight at 50°C.

Here is a chemical reaction formula: Reactants are:amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC;aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3, Reagents are:Base:C(=O)([O-])[O-].[K+].[K+];Solvent:CC1=CC=CC=C1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN1C[C@H](OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5=CC=CC=C5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: Charged a round-bottom flask with a mixture of 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (0.76 g, 3.72 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (1.022 g, 3.72 mmol), palladium (II) acetate (0.025 g, 0.11 mmol), rac-BINAP (0.116 g, 0.19 mmol), potassium carbonate (0.926 g, 6.70 mmol), and toluene (15 mL). The atmosphere was inerted through consecutive vacuum-nitrogen purge cycles, then heated at 110 °C under N2(g) for 16 hours. HPLC-UV shows a small percentage (3-6% depending on wavelength) of oxazepine remaining, aminopyridine if fully converted. The mixture was allowed to cool to room temperature. DCM and 2M HCl was added and the orgaic phase were removed. The aqueous phase were basified using solid KOH and a 4M solution. Extracted with DCM, dried oved MgSO4 and concentrated.

Here is a chemical reaction formula: Reactants are:amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC;aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3, Reagents are:Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[K+].[K+];metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN1C[C@H](OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5=CC=CC=C5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 2011-05-03; 16:30 Charged a round-bottom flask with a mixture of 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (16 g, 78.34 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (21.52 g, 78.34 mmol), palladium (II) acetate (0.528 g, 2.35 mmol), rac-BINAP (2.439 g, 3.92 mmol), potassium carbonate (19.49 g, 141.02 mmol), and toluene (200 mL). The atmosphere was inerted through consecutive vacuum-nitrogen purge cycles, then heated at 110 °C under N2(g). 2011-05-04; 10:52:55 HPLC-UV shows a small percentage (3-6% depending on wavelength) of oxazepine remaining, aminopyridine if fully converted. The mixture was allowed to cool to room temperature. DCM and 2M HCl was added and the orgaic phase were removed. The aqueous phase were basified using solid KOH, extracted with DCM and concentrated EN04644-87-001 (13 g, 29.4 mmol, 37.5 %) . The remaining organic phase was treated second time with HCl 2M, this aqueous phase contained also product ( 75% according with HPLC). The HCl solution was basified using KOH and extracted with DCM to give EN04644-87-002. EN04644-87-001 (13 g, 29.4 mmol, 37.5 %) (36g of crude) was dissolved in iPrOH (70mL) with heating and the slurry was left over a long weekend (4d). The precipitated obtained (after seeding with a sample from Jacob EN0) had 87% purity. The precipitated obtained (19g) were sent to for purification.

Here is a chemical reaction formula: Reactants are:amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC;aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3, Reagents are:Base:C(=O)([O-])[O-].[K+].[K+];Solvent:CC1=CC=CC=C1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN1C[C@H](OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5=CC=CC=C5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To a 250 mL roundbottomed flask was added 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (5.5 g, 23.11 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (6.50 g, 23.11 mmol), Palladium(II)acetate (0.157 g, 0.69 mmol), rac-BINAP (0.734 g, 1.16 mmol), Potassium carbonate (4.79 g, 34.66 mmol) and toluene (100 mL). The atmosphere was exchanged to nitrogen through consecutive vacuum- nitrogen purge cycles after which the mixture was heated at 120 °C for 16 h. Still some starting material left according to HPLC and LCMS (IPC 1), so another 25 mg of Pd(OAc)2 and 116 mg of BINAP was added, and heating continued. After another 4 h, no further progress was detected (IPC 2), so the mixture was allowed to cool to r.t. Dichloromethane (200 mL) was added and pH was adjusted to 2 by addition of 2M HCl (aq) (80 mL was added, but made too acidic). The phases were separated and the aq phase was made basic by addition of 1M NaOH (aq) (ca 70 mL). The aq phase was extracted with dichloromethane (200 mL) and re-extracted with another portion of dichloromethane (70 mL). Since the aq phase still contained some product, another portion of 1M NaOH (aq) (20 mL) was added and the aq phase was extracted with dichloromethane (100 mL). The combined organic layers were evaporated and toluene was added to co-evaporate water. The resulting brown solid was dried under vacuum o.n, yielding EN04391-37-001 (12 g, 27.1 mmol, 117 %). To the solid was added EtOAc (55 mL) and the slurry was stirred at r.t for 1 h. Stirring was turned off and the solid was allowed to sediment for 2 h. The solid was filtered off and washed with 2x 12 mL cold EtOAc, yielding EN04391-37-002 (5.7 g, 12.88 mmol, 55.7 %). The mother liquor still contained product so it was concentrated and to the residue was added isopropanol (18 mL, 2 mL/ g crude). The mixture was heated to dissolve everything (50 °C for 5 min) and was then stirred at r.t over night. A white precipitate had formed. The mixture was cooled on an ice bath (0-5 °C) for 1 h after which the solid was filtered off, washed with 2x10 mL cold isopropanol and dried at 40 °C under vacuum, yielding EN04391-37-003 (2.3 g, 5.20 mmol, 22.49 %). EN04391-37-002 and EN04391-37-003 were combined with EN04391-36-002 and EN04391-36-003 and further purified, see page EN04391-38.

Here is a chemical reaction formula: Reactants are:aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3;amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, Reagents are:metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[K+].[K+];Solvent:CC1=CC=CC=C1, and Products are 0:CN1C[C@H](OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5=CC=CC=C5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To a 250 mL roundbottomed flask was added 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (6 g, 25.21 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (7.10 g, 25.21 mmol), Palladium(II)acetate (0.171 g, 0.76 mmol), rac-BINAP (0.801 g, 1.26 mmol), Potassium carbonate (5.23 g, 37.81 mmol) and toluene (100 mL). The atmosphere was exchanged to nitrogen through consecutive vacuum- nitrogen purge cycles after which the mixture was heated at 120 °C for 18 h. Still some starting material left according to HPLC and LCMS (IPC 1), so another 25 mg of Pd(OAc)2 and 116 mg of BINAP was added, and heating continued. After another 3 h, approx. 2% starting material remained according to LCMS (IPC 2), so the mixture was allowed to cool to r.t. Dichloromethane (200 mL) was added and pH was adjusted to 2 by addition of 2M HCl (aq) (140 mL was added, but made too acidic). The phases were separated and the aq phase was made basic by addition of 1M NaOH (aq) (ca 200 mL). The aq phase was extracted with dichloromethane (200 mL) and re-extracted with another portion of dichloromethane (70 mL). Since an oily residue containing product had precipitated upon addition of acid/ base, the aq phase together with 100 mL dichloromethane was added to the residue in an attempt to dissolve it. More 1M NaOH (aq) was added to assure basic pH and the layers were separated. The combined organic layers were evaporated and the residue was dried under vacuum o.n. EN04391-36-001 (12.2 g, 27.6 mmol, 109 %) was obtained as a brown solid. To the solid was added isopropanol (48 mL, 4 mL/g crude prod) and the thick suspension was heated at 95 °C. After 30 min, the slurry was allowed to cool to r.t and left stirring over night. The still thick slurry was cooled on an ice bath at 0-5 °C for 1 h before it was filtered. The solid was washed with 4x15 mL of cold isopropanol and dried at 40 °C under vacuum o.n, yielding EN04391-36-002 (2.05 g, 4.63 mmol, 18.38 %) as a pale yellow solid The mother liquor that still contained product was concentrated. An orange- brown foam was obtained. Toluene was added and evaporated and the residue (8 g) was dissolved in MeCN (13.5 mL) and purified by chromatography (200 g SiO2 in a filter funnel, elutent: EtOAc (750 mL) followed by MeCN (1 L) and MeCN:MeOH 9:1 (1 L)). Fractions 10-13 were combined, concentrated and dried, yielding EN04391-36-003 (5.5 g, 12.43 mmol, 49.3 %) as a solid. EN04391-36-002 and EN04391-36-003 were further purified on page EN04391-38.

Here is a chemical reaction formula: Reactants are:amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC;aryl halide:CN1C[C@H](OC2=C(C1)C=CC(=N2)Cl)C3=CC=CC=C3, Reagents are:Base:CC(C)(C)[O-].[Na+];metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:CC1=CC=CC=C1, and Products are 0:CN1C[C@H](OC2=C(C1)C=CC(=N2)NC3=NC(=C(C=C3)C4=CN(N=C4)C)OC)C5=CC=CC=C5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (558 mg, 2.73 mmol), (R)-8-chloro-4-methyl-2-phenyl-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (750 mg, 2.73 mmol), Sodium tert-butoxide (394 mg, 4.09 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (119 mg, 0.19 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (175 mg, 0.19 mmol) were added to a microwave vial followed by toluene (11 mL). The reaction mixture was flushed with nitrogen and the mixture was heated to 100°C and stirred overnight. The reaction was complete. The solids were filtered off and washed with ethyl acetate. The organic solution was extracted by sat NaHCO3 solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography using DCM : [DCM:MeOH:NH3=90:10:1] = 100:0 to 10:90 as gradient. fr1 :160 mg approx 60% pure fr2: 804 mg purity 90-99% depending on wavelength, pH and solvent. Preparative purification with Gilson prep was performed on the combined mixture. 30-70% gradient was used. The first batch (38% of the crude) was lost due to the fact that the product gave **negative UV-signal** therefore didn't trigger any collection! The rest of the material was collected manually. The fractions were pooled together, concentrated in vacuo then tretaed with DCM and sat NaHCO3 solution. The phases were separated, the organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The product was obtained as white foam was dried overnight in a vacuum owen at 50°C.

Here is a chemical reaction formula: Reactants are:aryl halide:CC1=CC(=NC=C1)C2CN(CC3=C(O2)N=C(C=C3)Cl)C;amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC, Reagents are:metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Solvent:CC1=CC=CC=C1;Base:CC(C)(C)[O-].[Na+], and Products are 0:CC1=CC(=NC=C1)C2CN(CC3=C(O2)N=C(C=C3)NC4=NC(=C(C=C4)C5=CN(N=C5)C)OC)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (66.3 mg, 0.32 mmol), 8-chloro-4-methyl-2-(4-methylpyridin-2-yl)-2,3,4,5-tetrahydropyrido[3,2-f][1,4]oxazepine (94 mg, 0.32 mmol), Sodium tert-butoxide (46.8 mg, 0.49 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (20.20 mg, 0.03 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (14.85 mg, 0.02 mmol) were added to a microwave vial then toluene (2 mL) was added. The reaction mixture was flushed with nitrogen and the mixture was heated to 100°C and stirred overnight. The reaction was complete. The solids were filtered off and washed with DCM. The organic solution was extracted by sat NaHCO3 solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography using DCM : [DCM:MeOH:NH3=90:10:1] = 100:0 to 20:80 as gradient.

Here is a chemical reaction formula: Reactants are:amine:CN1C=C(C=N1)C2=C(N=C(C=C2)N)OC;aryl halide:CC1=CN=C(C=C1)C2CN(CC3=C(O2)N=C(C=C3)Cl)C, Reagents are:Solvent:CC1=CC=CC=C1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:CC(C)(C)[O-].[Na+], and Products are 0:CC1=CN=C(C=C1)C2CN(CC3=C(O2)N=C(C=C3)NC4=NC(=C(C=C4)C5=CN(N=C5)C)OC)C, please give me the reaction condition of this formula.

The condition of this chemical reaction is: 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (0.112 g, 0.55 mmol), 6-methoxy-5-(1-methyl-1H-pyrazol-4-yl)pyridin-2-amine (0.112 g, 0.55 mmol), Sodium tert-butoxide (0.079 g, 0.82 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.034 g, 0.05 mmol) and Tris(dibenzylideneacetone)dipalladium(0) (0.025 g, 0.03 mmol) were added to a microwave vial then toluene (3 mL) was added. The reaction mixture was flushed with nitrogen and the mixture was heated to 100°C and stirred overnight. The reaction was complete. The solids were filtered off and washed with DCM. The organic solution was extracted by sat NaHCO3 solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography using DCM : [DCM:MeOH:NH3=90:10:1] = 100:0 to 20:80 as gradient. Yellow foam.

Here is a chemical reaction formula: Reactants are:amine:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=C(C=C(C=C1F)Br)F, Reagents are:Solvent:C1COCCO1;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC(=C4)F)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: diacetoxypalladium (2.90 mg, 0.01 mmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (120 mg, 0.32 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (15.89 mg, 0.03 mmol), 1-bromo-3,5-difluorobenzene (46.5 µl, 0.40 mmol) and cesium carbonate (158 mg, 0.48 mmol) suspended in 1,4-dioxane (3184 µl). The resulting suspension was degased with argon and then stirred at 100 °C for 20 hours. The reaction mixture was allowed to cool to room temperature, The crude product was adsorbed on silica gel, the solvent was evaporated, and purified by flash chromatography on silica gel eluting with 0 to 10% methanol in ethyl acetate. The solvent was evaporated to dryness, the gum was triturated in Et2O/pentane to give a solid; the solid was filtered and dried to afford 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (80 mg, 51.2 %) as a white solid.

Here is a chemical reaction formula: Reactants are:amine:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3)OC(=CC2=O)N4CCOCC4;aryl halide:C1=C(C=C(C=C1F)Br)F, Reagents are:Solvent:C1COCCO1;metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CN(C)C(=O)C1=CC2=C(C(=C1)C3CCCN3C4=CC(=CC(=C4)F)F)OC(=CC2=O)N5CCOCC5, please give me the reaction condition of this formula.

The condition of this chemical reaction is: diacetoxypalladium (2.90 mg, 0.01 mmol) was added to a stirred mixture of N,N-dimethyl-2-morpholino-4-oxo-8-(pyrrolidin-2-yl)-4H-chromene-6-carboxamide (120 mg, 0.32 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (15.89 mg, 0.03 mmol), 1-bromo-3,5-difluorobenzene (46.5 µl, 0.40 mmol) and cesium carbonate (158 mg, 0.48 mmol) suspended in 1,4-dioxane (3184 µl). The resulting suspension was degased with argon and then stirred at 100 °C for 20 hours. The mixture was evaporated and diluted with DMF. The reaction mixture was purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford 8-(1-(3,5-difluorophenyl)pyrrolidin-2-yl)-N,N-dimethyl-2-morpholino-4-oxo-4H-chromene-6-carboxamide (77 mg, 49.3 %) as a beige solid.

Here is a chemical reaction formula: Reactants are:aryl halide:CCOC(=O)C1=CC=C(C=C1)Br;amine:C1CCNCC1, Reagents are:Solvent:C1COCCO1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CCOC(=O)C1=CC=C(C=C1)N2CCCCC2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: In a 250 mL round-bottomed flask was ethyl 4-bromobenzoate (816 µl, 5 mmol), piperidine (593 µl, 6.00 mmol), and CESIUM CARBONATE (2444 mg, 7.50 mmol) in dioxane (2.36E+04 µl) to give a white suspension. The solution was degassed with N2 (g) for 15 min and then added BINAP (156 mg, 0.25 mmol) and PALLADIUM(II) ACETATE (56.1 mg, 0.25 mmol). The reaction was heated to 100 °C and stirred under a reflux condenser overnight. The reaction was checked by LC-MS (complete), filtered, rinsed with DCM, concentrated in vacuo and onto silica gel. Purification by Iscos (25 g.) using 100% hexanes -> 40% EtOAc in Hexanes afforded a white solid. 950 mg of a white solid obtained. 1H NMR (300 MHz, DMSO- _d_ 6) d ppm 1.28 (t, _J_ =7.08 Hz, 3 H) 1.58 (s, 6 H) 3.31 - 3.38 (m, 4 H) 4.23 (q, _J_ =7.11 Hz, 2 H) 6.94 (m, _J_ =9.06 Hz, 2 H) 7.76 (m, _J_ =9.25 Hz, 2 H) LC-MS: Rt = 2.98 min. Method: Short Purity. MS ES+: 234.2 [M+H]+.

Here is a chemical reaction formula: Reactants are:amine:C1CCNCC1;aryl halide:CC(C)(C)OC(=O)C1=CN=C(C=C1)Br, Reagents are:Solvent:C1COCCO1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:CC(C)(C)OC(=O)C1=CN=C(C=C1)N2CCCCC2, please give me the reaction condition of this formula.

The condition of this chemical reaction is: In a 100 mL round-bottomed flask was tert-butyl 6-bromonicotinate (516 mg, 2 mmol), piperidine (237 µl, 2.40 mmol), and CESIUM CARBONATE (977 mg, 3.00 mmol) in dioxane (9763 µl) to give a white suspension. The solution was degassed with N2 (g) fo 20 mins. PALLADIUM(II) ACETATE (22.45 mg, 0.10 mmol) and BINAP (62.3 mg, 0.10 mmol) were added under N2 (g) and the reaction was heated to 100 °C. Start Time: 01-Jul-10 1:10:32 PM -0400. The reaction was checked by LC-MS (complete), filtered, rinsed with DCM, concentrated in vacuo. _02 July 2010_ Purification by Iscos (25 g) using 100% Hexanes -> 50% EtOAc in Hexanes afforded a white solid. 325 mg obtained. 1H NMR (300 MHz, DMSO- _d_ 6) d ppm 1.51 - 1.57 (m, 12 H) 1.57 - 1.77 (m, 5 H) 3.58 - 3.74 (m, 4 H) 6.78 - 6.92 (m, 1 H) 7.88 (dd, _J_ =9.16, 2.36 Hz, 1 H) 8.60 (dd, _J_ =2.45, 0.57 Hz, 1 H). LC-MS: Rt = 2.37 min. Method: Short Purity. MS ES+: 263.2 [M+H]+.

Here is a chemical reaction formula: Reactants are:amine:C1COCCN1;aryl halide:COC(=O)C1=CC(=CC(=C1)Br)C(=O)OC, Reagents are:metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CC1=CC=CC=C1;Base:C(=O)([O-])[O-].[Cs+].[Cs+], and Products are 0:COC(=O)C1=CC(=CC(=C1)N2CCOCC2)C(=O)OC, please give me the reaction condition of this formula.

The condition of this chemical reaction is: To a solution of dimethyl 5-bromoisophthalate (10 g, 36.62 mmol) in toluene (100 mL) where BINAP (2.5 g, 4.01 mmol), morpholine (4.4 g, 50.50 mmol), CESIUM CARBONATE (18 g, 55.25 mmol) and PALLADIUM(II) ACETATE (0.9 g, 4.01 mmol) added. The solution was heated to reflux under inert atm for 14h. The silvent was filtered and the filtrate was concentrated. The residue was purified by column chropmatography (Hep:EA) 1:1 to give dimethyl 5-morpholinoisophthalate (8.00 g, 78 %)

Here is a chemical reaction formula: Reactants are:amine:C1COCCN1;aryl halide:C1=C(C=NC=C1Br)Br, Reagents are:Base:CC(C)(C)[O-].[Na+];Solvent:CC1=CC=CC=C1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd], and Products are 0:C1COCCN1C2=CC(=CN=C2)Br, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A mixture of 3,5-dibromopyridine (3.01 mL, 12.66 mmol), morpholine (1.00 g, 11.48 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (0.210 g, 0.23 mmol), sodium 2-methylpropan-2-olate (1.655 g, 17.22 mmol) and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.429 g, 0.69 mmol) in degassed toluene (35 mL) was stirred for 16 hours at 110 °C in a sealed vessel under inert atmosphere. Extraction with sat. aq. Na2CO3 solution and AE, then back extraction 2x NaCl sat using DCM. The organics were dried over MgSO4 and evaporated _in vacuo_. The residue (see structure below, LC MS FLA-04227-45-02: 3,5 dimorpholino pyridine) was washed off with diethylether, then AE. The liquors were vaporated _in vacuo_. The residue was purified by chromatography (11 cm SiO2, diameter: 5 cm) eluent: AE/hex 25/75to 45/55 to provide 4-(5-bromopyridin-3-yl)morpholine (1.400 g, 50.2 %) as a yellow solid. 1H NMR, LC MS: FLA-04227-45-03. OK \---------------------------------------------------------

Here is a chemical reaction formula: Reactants are:aryl halide:C1=C(C=NC=C1Br)Br;amine:CNCCOC, Reagents are:Solvent:CC1=CC=CC=C1;metal and ligand:C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=C(C4=CC=CC=C4C=C3)C5=C(C=CC6=CC=CC=C65)P(C7=CC=CC=C7)C8=CC=CC=C8;metal and ligand:C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C1=CC=C(C=C1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd];Base:CC(C)(C)[O-].[Na+], and Products are 0:CN(CCOC)C1=CC(=CN=C1)Br, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A mixture of 3,5-dibromopyridine (1.468 mL, 6.17 mmol), 2-methoxy-N- methylethanamine (0.602 mL, 5.61 mmol), TRIS(DIBENZYLIDENEACETONE)DIPALLADIUM (0.103 g, 0.11 mmol), sodium 2-methylpropan-2-olate (0.809 g, 8.41 mmol) and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (0.175 g, 0.28 mmol) in degassed toluene (15 mL) was stirred for 16 hours at 90 °C in a sealed vessel under inert atmosphere. LC MS of the crude mixture: FLA 04227-53-01. Extraction with sat. aq. Na2CO3 solution and AE, then back extraction 2x NaCl sat using DCM. The organics were dried over MgSO4 and evaporated _in vacuo_. The residue was purified by chromatography (11 cm SiO2, diameter: 3.5 cm) eluent: AE/hex 25/75to 40/60 to provide 5-bromo-N-(2-methoxyethyl)-N-methylpyridin-3-amine (0.930 g, 67.6 %) as a yellow oil. 1H NMR, LC MS: FLA-04227-53-02. OK

Here is a chemical reaction formula: Reactants are:amine:C1=CC(=CC=C1N)S(=O)(=O)N;aryl halide:COC1=CC(=NC=C1)Cl, Reagents are:Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd];Solvent:CN1CCCC1=O, and Products are 0:COC1=CC(=NC=C1)NC2=CC=C(C=C2)S(=O)(=O)N, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A mixture of 4-aminobenzenesulfonamide (190mg, 1.10 mmol), 2-chloro-4-methoxypyridine (135 mg, 0.94 mmol), diacetoxypalladium (13mg, 0.06 mmol), cesium carbonate (417mg, 1.28 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (50 mg, 0.09 mmol) in NMP (2.0 mL) was heated **in the microwave** for 10 min at 150 °C. LC MS crude mix. FLA-04227-80-01 showed no reaction. Another 30 min at 150°C in the microwave provided FLA-04227-80-02 (crude mix.). No product. **Discard.**

Here is a chemical reaction formula: Reactants are:aryl halide:C1=CC=C(C=C1)Br;amine:C1=CC(=CC=C1N)S(=O)(=O)N, Reagents are:Solvent:CC(=O)N(C)C;Base:C(=O)([O-])[O-].[Cs+].[Cs+];metal and ligand:CC1(C2=C(C(=CC=C2)P(C3=CC=CC=C3)C4=CC=CC=C4)OC5=C1C=CC=C5P(C6=CC=CC=C6)C7=CC=CC=C7)C;metal and ligand:CC(=O)O.CC(=O)O.[Pd], and Products are 0:C1=CC=C(C=C1)NC2=CC=C(C=C2)S(=O)(=O)N, please give me the reaction condition of this formula.

The condition of this chemical reaction is: A mixture of 4-aminobenzenesulfonamide (100 mg, 0.58 mmol), bromobenzene (0.061 mL, 0.58 mmol),(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (26.9 mg, 0.05 mmol), diacetoxypalladium (5.21 mg, 0.02 mmol) and cesium carbonate (227 mg, 0.70 mmol) in degassed DMA (1.8 mL) was heated **_in the microwave_** for 20 min at 130 °C. LC MS FLA-04227-96-01 (pH extract 7-8) showed some product and a few bromobenzene left. Heating was continued for 15 min at 150°C. LC MS FLA-04227-96-02 (pH extract 7-8) showed reaction stalled. Reaction was stopped. Extraction with AE + ethanol / aq. sat NH4Cl (pH7), then back extraction with DCM.The organics were dried over MgSO4 and concentrated _in vacuo._ The crude product was adsorbed on silica gel 40-60µm and purified by flash chromatography on silica gel 15-40µm eluting with 2 % of ethanol in dichloromethane (NH3 0.5 %) to provide 4-(phenylamino)benzenesulfonamide (60.0 mg, 41.6 %) as a gum. 1H NMR, LC MS FLA-04227-96-03: OK **_Note: the product still contains 24% mol DMA_** **_Corrected yield: 30%_**