Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1([C:6]([OH:19])([C:17]#[CH:18])[CH2:7][C:8]2[O:13][C:12]([CH3:15])([CH3:14])[O:11][C:10](=[O:16])[CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.Br[C:21]1[S:22][CH:23]=[CH:24][N:25]=1.C(NC(C)C)(C)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C=O)C>[CH:1]1([C:6]([OH:19])([C:17]#[C:18][C:21]2[S:22][CH:23]=[CH:24][N:25]=2)[CH2:7][C:8]2[O:13][C:12]([CH3:15])([CH3:14])[O:11][C:10](=[O:16])[CH:9]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Brc1nccs1
Reactant: C#CC(O)(CC1=CC(=O)OC(C)(C)O1)C1CCCC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CN(C)C=O
Solvent: CC(C)NC(C)C
Product: CC1(C)OC(=O)C=C(CC(O)(C#Cc2nccs2)C2CCCC2)O1
Yield: 81 %

Procedure:
To a degassed solution of 6-(2-cyclopentyl-2-hydroxy-but-3-ynyl)-2,2-dimethyl-[1,3]dioxin-4-one (264.1 mg, 1.0; prepared as described in Example 1, Step 2), 2-bromothiazole (99.1 μL, 1.1 mmol), diisopropylamine (1.5 mL), and DMF (0.5 mL), under argon, was added Pd(PPh3)2Cl2 (28.1 mg, 0.04 mmol) and Cul (15.2 mg, 0.08 mmol). The resulting mixture was vacuum-flushed with argon (3×), then placed in 100° C. oil bath for 5 minutes, during which time the reaction becomes black/brown in color. The mixture was filtered through a plug of silica eluted with ethylacetate, concentrated, and purified by flash chromatography using 30% EtOAc/Hex as the eluent. The yield of product was 280 mg (81% yield). 1H NMR (CDCl3): δ 1.63 (m, 4H), 1.72 (s, 3H), 1.73 (s, 3H), 2.23 (pentet, 1H, J=8.0 Hz), 2.54 (s, 1H), 2.65 (s, 2H), 3.81 (s, 3H), 5.47 (s, 1H), 6.83 (d, 2H, J=8.7 Hz), 7.31(d, 2H, J=8.1 Hz), ESIMS (M+Na+): 393.2.
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([N+:13]([O-])=O)=[CH:9][N:8]=2)=[C:4]([CH3:18])[CH:3]=1.[H][H]>C(O)C.[OH-].[OH-].[Pd+2]>[Cl:1][C:2]1[CH:17]=[CH:16][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][N:8]=2)=[C:4]([CH3:18])[CH:3]=1
Reactant: [H][H]
Reactant: Cc1cc(Cl)ccc1Oc1ccc([N+](=O)[O-])cn1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CCO
Product: Cc1cc(Cl)ccc1Oc1ccc(N)cn1

Procedure:
2-(4-chloro-2-methyl-phenoxy)-5-nitropyridine (203 mg, 0.77 mmol) was dissolved in 95% ethanol (3 mL) and treated with 20% palladium hydroxide on carbon (50 mg). The reaction mixture was shaken in a hydrogen atmosphere (40 psi) for 1 hour. The solution was filtered through celite and concentrated in vacuo . MS (m/z): 234/236 (M+H)+; C12H11N2OCl requires 234.7.
Reaction SMILES: C(N(CC)CC)C.[F:8][C:9]([F:21])([F:20])[O:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]=[C:18]=[O:19])=[CH:13][CH:12]=1.[OH:22][C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[O:26][C:25](=[O:33])[CH:24]=1.Cl>CS(C)=O.O>[OH:22][C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[O:26][C:25](=[O:33])[C:24]=1[C:18](=[O:19])[NH:17][C:14]1[CH:13]=[CH:12][C:11]([O:10][C:9]([F:20])([F:21])[F:8])=[CH:16][CH:15]=1
Reactant: O=C=Nc1ccc(OC(F)(F)F)cc1
Reactant: O=c1cc(O)c2ccccc2o1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: O
Product: O=C(Nc1ccc(OC(F)(F)F)cc1)c1c(O)c2ccccc2oc1=O
Temperature: 25 °C
Reaction time: 5 h
Yield: 45.4 %

Procedure:
First 5.1 g (0.05 mol) of triethylamine and then, slowly, 10.2 g (0.05 mol) of 4-trifluoromethoxyphenyl isocyanate are added dropwise to 8.1 g (0.05 mol) of 4-hydroxycoumarin in 100 ml of dimethylsulphoxide at room temperature. The temperature thereby rises to 31° C. The reaction mixture is subsequently stirred at room temperature for 5 hours. It is added to a mixture of 250 ml of cold water and 15 ml of concentrated hydrochloric acid, whereupon a white precipitate separates out. The mixture is stirred for 30 minutes, with cooling, and the precipitate is filtered off with suction, rinsed with acid water and dried at 50° C. in vacuo. Recrystallization from 100 ml of dioxane gives 8.3 g (45.6% of theory) of 4-hydroxy-3-(4-trifluoromethyloxyphenyl-carbamoyl)-coumarin of melting point 194°-195° C.
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][C:7]([C:8](Cl)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[NH2:13][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][C:19]=1[OH:20].C([O-])([O-])=O.[Na+].[Na+].CC(O)=O>N1C=CC=CC=1.O>[OH:20][C:19]1[CH:18]=[CH:17][N:16]=[CH:15][C:14]=1[NH:13][C:8](=[O:9])[C:7]1[CH:11]=[CH:12][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=1
Reactant: Nc1cnccc1O
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: c1ccncc1
Solvent: CC(=O)O
Product: O=C(Nc1cnccc1O)c1ccc([N+](=O)[O-])cc1
Reaction time: 8 h
Yield: 61.5 %

Procedure:
A solution of p-nitrobenzoyl chloride (4.8 g, 25.7 mmol) in pyridine (77.0 mL) was added dropwise to a solution of 3-amino-4-hydroxypyridine (3.4 g, 30.9 mmol) in pyridine (51.0 mL) at 10° C. and stirred overnight. A solution of Na2CO3 (1.7 g) in water (65 mL) was added and the resultant mixture was stirred for 1 h. The reaction mixture was neutralized with 10% AcOH. The precipitate was collected by filtration, washed with 10% AcOH, and dried in vacuo (50° C.) to afford N-(4-hydroxypyridin-3-yl)-4-nitrobenzamide as a light green powder (4.1 g, Yield: 62%). 1HNMR (400 MHz, DMSO-d6) δ: 11.64 (1H, br s), 9.57 (1H, s), 9.07 (1H, s), 8.75 (1H, d, J=4.4 Hz), 8.36 (1H, d, J=8.8 Hz), 8.20 (1H, d, J=8.8 Hz), 7.74 (1H, d, J=4.4 Hz), 6.33 (1H, s); MS (ESI) calcd for C12H9N3O (m/z): 211. found: 212 [M+1]+.
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:12]=[CH:11][C:9]([OH:10])=[C:6]([O:7][CH3:8])[CH:5]=1)=[O:3].[OH-].[K+].[CH3:15][N:16]([CH3:20])[C:17](Cl)=[S:18]>O.C1COCC1.[OH-].[Na+]>[C:2]([C:4]1[CH:12]=[CH:11][C:9]([O:10][C:17](=[S:18])[N:16]([CH3:20])[CH3:15])=[C:6]([O:7][CH3:8])[CH:5]=1)(=[O:3])[CH3:1]
Reactant: CN(C)C(=S)Cl
Reactant: COc1cc(C(C)=O)ccc1O
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: COc1cc(C(C)=O)ccc1OC(=S)N(C)C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of acetovanillone (8.31 g, 50 mmol) and 2.81 g KOH (50 mmol) in H2O (34 mL), at 0°, is added a solution of dimethylthiocarbamoyl chloride (8.28 g, 67 mmol) in THF (14 mL), dropwise, at such a rate as to keep the reaction temperature below 12°. The reaction mixture is warmed to room temperature, and stirred for 30 minutes. It is then diluted with 1 N NaOH (100 mL) and extracted with EtOAc (3×80 mL). The combined organic phase is washed with H2O (1×100 mL) and brine (1×50 mL), dried over MgSO4, and concentrated in vacuo to give dimethylthiocarbamic acid O-(4-acetyl-2-methoxy-phenyl) ester. To a thick walled pyrex tube is aded dimethylthiocarbamic acid O-(4-acetyl-2-methoxy-phenyl) ester (9.81 g, 38.77 mmol). The tube is flushed with nitrogen, sealed, and then heated to 250° for 1 hour. After cooling, the residue is chromatographed (silica gel, 1:1 EtOAc/hexane) to yield dimethylthiocarbamic acid S-(4-acetyl-2-methoxy-phenyl) ester.
Reaction SMILES: Br[CH:2]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13][CH2:12]2)=[CH:7][CH:6]=1)=O.[CH3:29][C:30]1[N:35]=[N:34][C:33]([NH2:36])=[CH:32][CH:31]=1.C(N(CC)C(C)C)(C)C>C(O)(C)C>[CH3:29][C:30]1[CH:31]=[CH:32][C:33]2[N:34]([C:2]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[C:3]([C:5]3[CH:10]=[CH:9][C:8]([C:11]4([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13][CH2:12]4)=[CH:7][CH:6]=3)[N:36]=2)[N:35]=1
Reactant: Cc1ccc(N)nn1
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(C(=O)C(Br)c3ccccc3)cc2)CCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(C)O
Product: Cc1ccc2nc(-c3ccc(C4(NC(=O)OC(C)(C)C)CCC4)cc3)c(-c3ccccc3)n2n1

Procedure:
A mixture of crude tert-butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-1-A (1.00 g, ˜80% purity, 1.87 mmol, 1.0 eq), 6-methylpyridazin-3-amine (CAS-Nr. 18591-82-7, 0.245 g, 2.24 mmol, 1.2 eq), N,N-diisopropylethylamine (0.33 mL, 1.87 mmol, 1.0 eq) and activated 3 Å molecular sieves in isopropanol (5.7 mL) was heated for 7 hours under reflux. On cooling, the mixture was partitioned between DCM and water, stirred vigorously and filtered through a silicone coated filter paper. The filtrate was concentrated in vacuo. UPLC analysis of the crude product indicated a purity of >90%. The crude product was used in the next step without further purification.
Reaction SMILES: [CH2:1]([O:21][CH2:22][C@H:23]([CH2:25][OH:26])[OH:24])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].[C:27]1([C:33]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)Cl)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.O1CCCC1.C(#N)C>C(N(CC)CC)C>[CH2:1]([O:21][CH2:22][C@H:23]([CH2:25][O:26][C:33]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)([C:41]1[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1)[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)[OH:24])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: CCCCCCCCCCCCCCCCCCCCOC[C@@H](O)CO
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CC#N
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCCCCCCCCCCCCCCCCCCCOC[C@@H](O)COC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Yield: 78.8 %

Procedure:
20 grams of 1-eicosanyl-sn-glycerol and 18 grams of triphenylchloromethane were added to a mixture of 400 ml dry tetrahydrofuran (THF) and 100 ml dry acetonitrile. 15 ml of dry triethylamine was added, and the reaction mixture was refluxed for 17 hours. The reaction mixture was then cooled to room temperature, poured on ice (500 grams), transferred to a separatory funnel, and extracted thrice with 200 ml diethyl ether. The organic phase was washed consecutively with 150 ml water, twice with 150 ml dilute (1.5%) H2SO4, 150 ml water, 150 ml concentrated aqueous sodium bicarbonate, and again with 150 ml water. The solution was then dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The obtained residue, a brown oil, was dissolved in 300 ml ethyl acetate, and cooled at −20° C. overnight. The mixture was centrifuged (3,500 rotations per minute) at −10° C., and the mother liquid was poured of. The obtained solid was dissolved in hexane and refrigerated (5±3° C.) overnight. Filtration of the precipitate yielded 26.0 grams of pure (R)-1-eicosanyl-3-trityl-sn-glycerol as an off-white solid. The yield was 79%.
Reaction SMILES: [Cl:1][C:2]1[C:7]2[CH2:8][CH2:9][N:10]([CH3:13])[CH2:11][CH2:12][C:6]=2[C:5]([CH2:14][CH2:15][CH2:16]O)=[CH:4][CH:3]=1.S(Cl)([Cl:20])=O>C(Cl)Cl>[ClH:1].[Cl:1][C:2]1[C:7]2[CH2:8][CH2:9][N:10]([CH3:13])[CH2:11][CH2:12][C:6]=2[C:5]([CH2:14][CH2:15][CH2:16][Cl:20])=[CH:4][CH:3]=1
Reactant: CN1CCc2c(Cl)ccc(CCCO)c2CC1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: CN1CCc2c(Cl)ccc(CCCCl)c2CC1
Product: Cl
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of 9-chloro-2,3,4,5-tetrahydro-3-methyl-1H-3-benzazepine-6-propanol (0.8 g, 3 mmol) in methylene chloride (30 ml) was stirred at 5° C. and treated with thionyl chloride (40 ml). The mixture was stirred for 10 minutes at 5° C., 15 minutes at 25° C., 3 hours at 55° C. and 16 hours at 25° C. The mixture was concentrated to give 0.96 g of 6-chloro-9-(3-chloropropyl)-2,3,4,5-tetrahydro-3-methyl-1H-3-benzazepine hydrochloride.
Reaction SMILES: C([Mg]Cl)CCC.C([Li])CCC.Br[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[N:14]=1.[S:20](Cl)(Cl)(=[O:22])=[O:21].[C:25]1([OH:31])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(CC)CC)C>C1(C)C=CC=CC=1.C(#N)C>[Br:19][C:15]1[N:14]=[C:13]([S:20]([O:31][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)(=[O:22])=[O:21])[CH:18]=[CH:17][CH:16]=1
Reactant: O=S(=O)(Cl)Cl
Reactant: Brc1cccc(Br)n1
Reactant: Oc1ccccc1
Agent: CCCC[Mg]Cl
Agent: [Li]CCCC
Solvent: CC#N
Solvent: CCN(CC)CC
Solvent: Cc1ccccc1
Product: O=S(=O)(Oc1ccccc1)c1cccc(Br)n1
Temperature: -10 °C
Reaction time: 2 h

Procedure:
n-Butyl magnesium chloride (2.0 M in THF, 2.25 ml, 45 mmol) was added to a stirred solution of n-butyl lithium (1.6 M in hexanes, 5.56 ml, 8.9 mmol) at 0° C. under argon. After 10 minutes at 0° C. the mixture was cooled to −10° C. A solution of 2,6-dibromopyridine (3.0 g, 12.7 mmol) in toluene (35 ml) was added over 10 minutes and the mixture was stirred at −10° for 2 hours. After cooling to −40° C., sulfur dioxide gas was bubbled into the mixture for 5 minutes and the reaction was stirred at −40° C. for 30 minutes. Sulfuryl chloride (1.1 ml, 13.6 mmol) was added and the mixture was allowed to warm to room temperature. The resulting mixture was added over 5 minutes to a stirred mixture of phenol (1.25 g, 13.3 mmol) and triethylamine (7.0 ml, 50.6 mmol) in acetonitrile (30 ml) at 0° C. The mixture was stirred at 0° C. for 30 minutes and then at room temperature for 2 hours. The mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and dilute sodium bicarbonate solution. The organic phase was washed with water, brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to afford the title product (D7). MS (ES+) m/e 314/316 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]2[O:8][C:9]3[C:14]([C@H:15]([C:16]([CH3:21])([CH3:20])[C:17](O)=[O:18])[C:5]2=[CH:4][CH:3]=1)=[CH:13][CH:12]=[CH:11][CH:10]=3.C(N(CC)CC)C.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.[S:53]1[CH:57]=[N:56][N:55]=[C:54]1[NH2:58].Cl>C(#N)C.CCO>[Cl:1][C:2]1[N:7]=[C:6]2[O:8][C:9]3[C:14]([C@H:15]([C:16]([CH3:21])([CH3:20])[C:17]([NH:58][C:54]4[S:53][CH:57]=[N:56][N:55]=4)=[O:18])[C:5]2=[CH:4][CH:3]=1)=[CH:13][CH:12]=[CH:11][CH:10]=3
Reactant: Nc1nncs1
Reactant: CC(C)(C(=O)O)[C@H]1c2ccccc2Oc2nc(Cl)ccc21
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: CCO
Solvent: CC#N
Product: CC(C)(C(=O)Nc1nncs1)[C@H]1c2ccccc2Oc2nc(Cl)ccc21
Temperature: 80 °C
Yield: 78.6 %

Procedure:
To a soln. of (S)-2-(2-chloro-5H-chromeno[2,3-b]pyridin-5-yl)-2-methylpropanoic acid (30b, 10 g, 32.9 mmol) in acetonitrile (200 ml) was added triethylamine (22.94 ml, 165 mmol), O-(7-AZABENZOTRIAZOL-1-YL)-N,N,N′,N′-TETRAMETHYLURONIUM PF6 (HATU) (16.27 g, 42.8 mmol) and 1,3,4-thiadiazol-2-amine (9.99 g, 99 mmol). The resulted mixture was heated at 80° C. for 12 h. The reaction mixture was then concentrated in vacuum and the residue was partitioned between EtOAc and 1N HCl. The obtained organic layer was washed with saturated NaHCO3, brine, then dried (Na2SO4) and concentrated to give a solid. The solid was dissolved in EtOH (400 mL) with gentle warming. Added 1N HCl (˜200 mL) portionwise. The solid was collected and washed with water, dried on vacuum pump overnight to give 10 g (79%) of (S)-2-(2-chloro-5H-chromeno[2,3-b]pyridin-5-yl)-2-methyl-N-(1,3,4-thiadiazol-2-yl)propanamide (53a). MS (E+) m/z: 387 (M+H); LC retention time: 3.12 min.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:26])[C:9]([C:15]2[CH:16]=[CH:17][C:18]3[O:22][C:21](=[O:23])[N:20]([CH3:24])[C:19]=3[CH:25]=2)([OH:14])[C:10]([F:13])([F:12])[F:11])=[C:4]([C:27]([F:30])([F:29])[F:28])[CH:3]=1.[F:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][C:37]=1[C:38]([O:40][CH3:41])=[O:39]>>[CH3:41][O:40][C:38]([C:37]1[CH:36]=[CH:35][C:34]([C:2]2[CH:7]=[CH:6][C:5]([CH:8]([CH3:26])[C:9]([OH:14])([C:15]3[CH:16]=[CH:17][C:18]4[O:22][C:21](=[O:23])[N:20]([CH3:24])[C:19]=4[CH:25]=3)[C:10]([F:12])([F:13])[F:11])=[C:4]([C:27]([F:29])([F:30])[F:28])[CH:3]=2)=[CH:33][C:32]=1[F:31])=[O:39]
Reactant: COC(=O)c1ccc(B(O)O)cc1F
Reactant: CC(c1ccc(Br)cc1C(F)(F)F)C(O)(c1ccc2oc(=O)n(C)c2c1)C(F)(F)F
Product: COC(=O)c1ccc(-c2ccc(C(C)C(O)(c3ccc4oc(=O)n(C)c4c3)C(F)(F)F)c(C(F)(F)F)c2)cc1F

Procedure:
The title compound was prepared in analogy to Example 117 from 5-[2-(4-bromo-2-trifluoromethyl-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-3-methyl-3H-benzooxazol-2-one (obtained in Example 193, step 3) by Suzuki coupling with 3-fluoro-4-methoxycarbonyl-benzeneboronic acid [CAS Reg. No. 505083-04-5]. MS (m/e)=572.1 [M+H+].
Reaction SMILES: C([NH:4][C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][C:13]=1[N+:14]([O-:16])=[O:15])[C:8]([OH:10])=O)(=O)C.[C:17]1([S:23]([NH2:26])(=[O:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C1(C2CCCCCCCCCC=2)CCCCCCCCNN=1>CN(C)C=O>[C:17]1([S:23]([NH:26][C:8](=[O:10])[C:7]2[CH:11]=[CH:12][C:13]([N+:14]([O-:16])=[O:15])=[C:5]([NH2:4])[CH:6]=2)(=[O:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CC(=O)Nc1cc(C(=O)O)ccc1[N+](=O)[O-]
Reactant: NS(=O)(=O)c1ccccc1
Agent: C1=C(C2=NNCCCCCCCC2)CCCCCCCCC1
Solvent: CN(C)C=O
Product: Nc1cc(C(=O)NS(=O)(=O)c2ccccc2)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
N,N′-carbonyldiimidazole (28.9 g) was added to a solution of 20.0 g of 3-acetylamino-4-nitrobenzoic acid in 300 ml of N,N-dimethylformamide, and the mixture was stirred at room temperature for 1 hour. Further, 28.00 g of benzenesulfonamide and 27.16 g of diazabicycloundecene were added thereto, and the mixture was stirred at 100° C. for 4 days. The solvent was distilled off under reduced pressure. Chloroform and a 10% sodium hydroxide aqueous solution were added to the residue, and the mixture was vigorously stirred. The aqueous layer was neutralized with 10% hydrochloric acid, and the mixture was vigorously stirred with the addition of chloroform. The crystals precipitated were separated through filtration, and were dried to 14.4 g of N-benzenesulfonyl-3-amino-4-nitrobenzamide.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([OH:9])[CH:4]=1.F[C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:21])[CH3:20])=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C(=O)C>O>[F:1][C:2]([F:10])([F:11])[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][C:13]2[CH:18]=[CH:17][C:16]([C:19](=[O:21])[CH3:20])=[CH:15][CH:14]=2)[CH:4]=1
Reactant: Oc1cccc(C(F)(F)F)c1
Reactant: CC(=O)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: CC(=O)c1ccc(Oc2cccc(C(F)(F)F)c2)cc1

Procedure:
A mixture of 32.4 g of α,α,α-trifluoro-m-cresol, 27.62 g of p-fluoroacetophenone, 55.2 g of potassium carbonate and 250 ml of N,N-dimethylacetamide is heated under Argon overnight with vigorous stirring at 150°-155° C. After cooling the mixture is added to 500 ml of water and extracted with benzene. The combined extracts are washed with two 100 ml portions of 5% NaOH, 100 ml of H2O, 100 ml of saturated brine, and dried over MgSO4. Evaporation of the solvent at reduced pressure affords a brown liquid which is distilled to give the product as a pale yellow oil (bp 122°-142° C. @ 0.2 mm).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:20](=[O:21])[C:11]3=[N:12][NH:13][C:14]4[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=4[C:10]3=[N:9]2)=[CH:4][CH:3]=1.[H][H]>FC(F)(F)C(O)=O.[Pt]=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:20](=[O:21])[C:11]3=[N:12][NH:13][C:14]4[CH2:15][CH2:16][CH2:17][CH2:18][C:19]=4[C:10]3=[N:9]2)=[CH:4][CH:3]=1
Reactant: O=c1c2n[nH]c3ccccc3c-2nn1-c1ccc(Cl)cc1
Reactant: [H][H]
Agent: O=[Pt]
Solvent: O=C(O)C(F)(F)F
Product: O=c1c2n[nH]c3c(c-2nn1-c1ccc(Cl)cc1)CCCC3

Procedure:
To 2-(4-chlorophenyl)-2,5-dihydropyrazolo[4,3-c]cinnolin-3-one (0.5 g) dissolved in trifluoroacetic acid (20 ml) was added platinum oxide (0.2 g). The re action mixture was hydrogenated at 50 psi until no further uptake of hydrogen was observed. The catalyst was collected by filtration, the filtrate was poured onto ice and basified with ammonia. On the addition of dichloromethane a solid precipitated out; the solid was collected by filtration, washed with water and dried. Recrystallisation from ethanol gave the title compound. δH (360 MHz; DMSO-d6) 1.83 (4H, m, CH2), 2.67 (2H, t, J=5.7 Hz, CH2), 2.75 (2H, t, J=5.7 Hz, CH2), 7.51 (2H, d, J=9 Hz, ArH), 8.23 (2H, d, J=9 Hz, ArH), m/z (ESP+) 301/303 (MH+).
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC([O:24][CH:25]([CH3:27])C)=O.O[CH2:35][C:36]1[CH:41]=[CH:40][N:39]=[CH:38][C:37]=1[CH3:42].[S:43]1C=CC=C1CC(O)=O>C1COCC1.C(OCC)(=O)C.CCCCCC>[C:25]([S:43][CH2:35][C:36]1[CH:41]=[CH:40][N:39]=[CH:38][C:37]=1[CH3:42])(=[O:24])[CH3:27]
Reactant: O=C(O)Cc1cccs1
Reactant: CC(C)OC(=O)N=NC(=O)OC(C)C
Reactant: Cc1cnccc1CO
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: CC(=O)SCc1ccncc1C
Temperature: 0 °C
Reaction time: 1 h
Yield: 118.8 %

Procedure:
To an ice-cold, mechanically stirred solution of triphenylphosphine (17.04 g, 0.065 mol) in 250 mL of dry THF was added dropwise diisopropyl azodicarboxylate (12.8 mL, 0.065 mol) and the resulting slurry was stirred at 0° C. for 1 h. To this mixture was added dropwise a solution of 4-hydroxymethyl-3-methylpyridine (4.0 g, 0.0325 mol) in 100 mL of dry THF, followed by freshly distilled thiolacetic acid (4.64 mL, 0.065 mol). The resulting mixture was stirred at 0° C. for 1 h and then at room temperature for 1 h to give an orange solution. The solution was concentrated (rotary evaporator) and then diluted with petroleum ether. The resulting mixture was filtered and the filtrate was evaporated to give an orange oil. Chromatography (silica gel/hexane then 10%→50% ethyl acetate-hexane) of this oil gave 7.0 g of a oil which was distilled (Kugelrohr) to give the pure product (6.0 g, 100%) as a yellow oil, b.p. (air-bath temperature) 95°-100° C./0.1 torr: 1Hnmr (CDCl3) δ8.40, 7.20 (ABq, J=5Hz, 2H), 8.37 (s, 1H), 4.08 (s, CH2), 2.35 (s, CH3), 2.32 (s, CH3); ir (neat) 1695 cm-1.
Reaction SMILES: [CH:1]([N:3]1CCC[C:4]1=O)=C.[CH:9]([CH:11]1[CH2:18][CH2:17][CH2:16][CH2:15][NH:14][C:12]1=[O:13])=C.CN(CCCC=C(C)C(N)=O)C.[C:31]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])(=[O:35])[C:32]([CH3:34])=[CH2:33]>C(O)C>[CH3:9][C:11]([C:12]([NH:14][CH2:15][CH2:16][CH2:17][N:3]([CH3:4])[CH3:1])=[O:13])=[CH2:18].[C:31]([O:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH3:54])(=[O:35])[C:32]([CH3:34])=[CH2:33]
Reactant: C=CC1CCCCNC1=O
Reactant: C=CN1CCCC1=O
Agent: C=C(C)C(=O)OCCCCCCCCCCCCCCCCCC
Agent: CC(=CCCCN(C)C)C(N)=O
Solvent: CCO
Product: C=C(C)C(=O)NCCCN(C)C
Temperature: 68 °C
Reaction time: 5 h

Procedure:
Vinyl pyrrolidone (55.6 g), vinyl caprolactam (577.5 g), dimethylaminopropyl methacrylamide (DMAPMA) (42.6 g), n-octadecyl methacrylate (33.9 g) and ethanol (867.2 g) were charged into a 2-liter water-jacketed resin flask. The reaction flask was equipped with a condenser, a thermometer, a septum (for catalyst addition), an anchor-type metal stirrer, and a nitrogen sparge tube. Nitrogen was bubbled through the solution while the resin flask was heated to 68° C. using hot water circulating through the jacketed flask. After an additional half-hour of degassing at reflexing, a first shot of Lupersol 11 (0.25 ml) was injected into the flask. Subsequently, Lupersol 11 additions were made at 10, 40, 70, 100, 140, 180 and 240 minutes after the first addition. The reaction temperature was then brought up to 75° C. and held for an additional 5 hours, then cooled to room temperature and discharged.