Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:3]=1[C:4]([NH:6][C:7]1[CH:34]=[CH:33][C:10]([C:11]([N:13]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[C:17]3=[N:24][N:25]([CH2:27][C:28]([O:30]CC)=[O:29])[CH:26]=[C:16]3[CH2:15][CH2:14]2)=[O:12])=[CH:9][CH:8]=1)=[O:5].O1CCCC1.[OH-].[Na+].Cl>C(O)C>[Cl:1][C:2]1[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:3]=1[C:4]([NH:6][C:7]1[CH:34]=[CH:33][C:10]([C:11]([N:13]2[C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=3[C:17]3=[N:24][N:25]([CH2:27][C:28]([OH:30])=[O:29])[CH:26]=[C:16]3[CH2:15][CH2:14]2)=[O:12])=[CH:9][CH:8]=1)=[O:5]
Reactant: CCOC(=O)Cn1cc2c(n1)-c1ccccc1N(C(=O)c1ccc(NC(=O)c3ccc(Cl)cc3Cl)cc1)CC2
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: O=C(O)Cn1cc2c(n1)-c1ccccc1N(C(=O)c1ccc(NC(=O)c3ccc(Cl)cc3Cl)cc1)CC2
Temperature: 25 °C
Reaction time: 6 h
Yield: 0.1 %

Procedure:
To a stirred slurry of 0.477 g of 6-[4-[(2,4-dichlorobenzoyl)amino]benzoyl]-5,6-dihydropyrazolo-[4,3-d][1]benzazepine-2 (4H)-acetic acid, ethyl ester in 15 ml of ethyl alcohol is added 5 ml of tetrahydrofuran followed by 1.30 ml of 1M NaOH. The reaction mixture is stirred at room temperature for 6 hours followed by the addition of 0.750 ml of 2N HCl. The acidic reaction mixture is evaporated in vacuo, triturated with CHCl3, combined, treated with activated carbon, filtered through MgSO4 and evaporated in vacuo to give 0.380 mg of the desired product as a clear foam.
Reaction SMILES: Br[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18](B(O)O)=[CH:17][CH:16]=1.[F-].[Cs+].O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:13][O:14][C:15]1[CH:20]=[CH:19][C:18]([C:2]2[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=2)=[CH:17][CH:16]=1
Reactant: CCOC(=O)c1ccc(Br)cc1
Reactant: COc1ccc(B(O)O)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cs+]
Agent: [F-]
Solvent: COCCOC
Solvent: O
Product: CCOC(=O)c1ccc(-c2ccc(OC)cc2)cc1
Temperature: 85 °C

Procedure:
A stirred mixture of 4-bromobenzoic acid, ethyl ester (23.6 g, 103 mmol), 4-methoxyphenylboronic acid (15.6 g, 103 mmol), tetrakis(triphenylphosphine)palladium (0) (2.0 g, 1.73 mmol) and powdered caesium fluoride (30.0 g, 200 mmol) in 1,2-dimethoxyethane (300 mL) is heated at 85° C. for 3 h. The mixture is then treated with water (500 mL) and extracted with ethyl acetate (3×100 mL). The combined extracts are washed (saturated NaCl), dried (Na2SO4), filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by chromatography (silica gel, 5% ethyl acetate/95% cyclohexane) to 4′-methoxy-[1,1′-biphenyl]-4-carboxylic acid, ethyl ester as a colourless crystalline solid. m.p. 103-104° C.
Reaction SMILES: [CH2:1]([N:4]1[CH2:8][CH2:7][CH2:6][CH2:5]1)[C:2]#[CH:3].C(NC(C)C)(C)C.I[C:17]1[CH:22]=[CH:21][C:20](/[C:23](/[C:40]2[CH:45]=[CH:44][C:43]([C:46]3[S:47][C:48]([CH3:51])=[CH:49][CH:50]=3)=[CH:42][CH:41]=2)=[CH:24]\[CH2:25][O:26][C:27]2[CH:38]=[CH:37][C:30]([O:31][CH2:32][C:33]([O:35][CH3:36])=[O:34])=[C:29]([CH3:39])[CH:28]=2)=[CH:19][CH:18]=1>O1CCCC1.[Cu]I.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>[CH3:39][C:29]1[CH:28]=[C:27]([O:26][CH2:25]/[CH:24]=[C:23](/[C:40]2[CH:41]=[CH:42][C:43]([C:46]3[S:47][C:48]([CH3:51])=[CH:49][CH:50]=3)=[CH:44][CH:45]=2)\[C:20]2[CH:21]=[CH:22][C:17]([C:3]#[C:2][CH2:1][N:4]3[CH2:8][CH2:7][CH2:6][CH2:5]3)=[CH:18][CH:19]=2)[CH:38]=[CH:37][C:30]=1[O:31][CH2:32][C:33]([O:35][CH3:36])=[O:34]
Reactant: C#CCN1CCCC1
Reactant: COC(=O)COc1ccc(OC/C=C(\c2ccc(I)cc2)c2ccc(-c3ccc(C)s3)cc2)cc1C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: COC(=O)COc1ccc(OC/C=C(\c2ccc(C#CCN3CCCC3)cc2)c2ccc(-c3ccc(C)s3)cc2)cc1C
Temperature: 25 °C
Reaction time: 2.5 h

Procedure:
1-Propargylpyrrolidine (168 mg, 1.54 mmol) and diisopropylamine (0.27 mL, 1.93 mmol) were added to a solution of methyl (Z)-[4-[3-(4-iodophenyl)-3-[4-(5-methylthiophen-2-yl)phenyl]allyloxy]-2-methylphenoxy]acetate (235 mg, 0.385 mmol; prepared as described in example 17) in tetrahydrofuran (5 mL). The mixture was degassed and copper(I) iodide (15 mg, 0.079 mmol) and bis(triphenylphosphine)-palladium(II) dichloride (27 mg, 0.038 mmol) were added. The reaction mixture was stirred at ambient temperature for 2.5 h and subsequently evaporated in vacuo. The residue was purified by flash column chromatography (silica gel Fluka 60, dichloromethane/methanol 98:2+0.5% of triethylamine) yielding methyl (E)-[2-methyl-4-[3-[4-(5-methylthiophen-2-yl)phenyl]-3-[4-[3-(pyrrolidin-1-yl)propynyl]phenyl]-allyloxy]phenoxy]acetate as brownish oil.
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]([CH3:15])[C:12]([OH:14])=[O:13])=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3].S(=O)(=O)(O)O.[CH2:21](O)[CH3:22]>>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([CH:11]([CH3:15])[C:12]([O:14][CH2:21][CH3:22])=[O:13])=[CH:9][CH:10]=1)[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)Cc1ccc(C(C)C(=O)O)cc1
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)C(C)c1ccc(CC(C)C)cc1
Temperature: 25 °C

Procedure:
Under a nitrogen atmosphere, 2-(4-isobutylphenyl)-propionic acid (15.0 g) was dissolved in ethanol (200 ml), and conc. sulfuric acid (1 ml) was added, after which the solution was stirred with heating under reflux for 15 hours. The reaction mixture was cooled to room temperature, concentrated under reduced pressure, diluted with ethyl acetate, and thereafter neutralized with a saturated aqueous sodium bicarbonate solution. After extraction with ethyl acetate, the organic layer was dried over sodium sulfate and then concentrated under reduced pressure to obtain ethyl 2-(4-isobutyl-phenyl)-propionate.
Reaction SMILES: [CH3:1][O:2][CH:3]([O:15][CH3:16])[C:4]1[N:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][NH:11]2)=[CH:6][C:5]=1[I:14].[C:17](=O)([O:25]C1C=CC=CC=1)[O:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C>C1COCC1>[CH3:16][O:15][CH:3]([O:2][CH3:1])[C:4]1[N:13]=[C:12]2[C:7]([CH2:8][CH2:9][CH2:10][N:11]2[C:17]([O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:25])=[CH:6][C:5]=1[I:14]
Reactant: COC(OC)c1nc2c(cc1I)CCCN2
Reactant: O=C(Oc1ccccc1)Oc1ccccc1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(OC)c1nc2c(cc1I)CCCN2C(=O)Oc1ccccc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 7-(dimethoxymethyl)-6-iodo-1,2,3,4-tetrahydro-1,8-naphthyridine (intermediate 52, 97 mg, 0.290 mmol) and diphenyl carbonate (74.6 mg, 0.348 mmol) in THF (2.5 ml) at −78° C. was treated with LHMDS (1 M in THF, 0.334 ml, 0.334 mmol) and stirred for 2 h. The reaction was then allowed to warm to room temperature over 20 min, quenched by addition of sat. aq. NH4Cl and extracted with DCM (2×). The organic layer was dried over Na2SO4, filtered and concentrated. The crude material was purified by normal phase chromatography (12 g silica gel cartridge, heptanes/EtOAc 100:0 to 0:100) to give the title compound as a white solid. (UPLC-MS 3) tR 1.19 min; ESI-MS 455.1 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([N+:9]([O-])=O)[C:5]([Cl:12])=[C:4]([Cl:13])[N:3]=1.[CH2:14]([O:21][C:22]([N:24]1[CH2:29][CH2:28][C@H:27]([CH2:30]N)[C@H:26]([OH:32])[CH2:25]1)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CN1CCOCC1>C1COCC1>[CH2:14]([O:21][C:22]([N:24]1[CH2:29][CH2:28][CH:27]([CH2:30][NH:9][C:6]2[C:7]([Cl:8])=[C:2]([Cl:1])[N:3]=[C:4]([Cl:13])[C:5]=2[Cl:12])[CH:26]([OH:32])[CH2:25]1)=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: NC[C@H]1CCN(C(=O)OCc2ccccc2)C[C@H]1O
Reactant: O=[N+]([O-])c1c(Cl)c(Cl)nc(Cl)c1Cl
Solvent: C1CCOC1
Solvent: CN1CCOCC1
Product: O=C(OCc1ccccc1)N1CCC(CNc2c(Cl)c(Cl)nc(Cl)c2Cl)C(O)C1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
2,3,5,6-tetrachloro-4-nitropyridine (S. M. Roberts et al., J. Chem. Soc. C, 2844–2848(1968)) (1.7 g, 6.5mmol) was added to a solution of (cis)-4-aminomethyl-3-hydroxy-piperidine-1-carboxylic acid benzyl ester (1.71 g, 6.49 mmol) and N-methylmorpholine (0.785 mL, 7.15 mmol) in THF (50 mL) at room temperature. The resulting reaction mixture was stirred for 18 h at room temperature then partitioned between EtOAc and water, The organic layer was washed with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate and the solvent evaporated to give crude product purified by flash column chromatography (20–80% EtOAc hexane) to give 3-hydroxy-4-[(2,3,5,6-tetrachloro-pyridin-4-ylamino)-methyl]-piperidine-1-carboxylic acid benzyl ester compound. M.S (M+1): 478.
Reaction SMILES: [F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4]([OH:13])=[CH:5][C:6](=[O:12])[S:7]2.C(N(CC)CC)C.[CH2:21]([O:23][C:24](=[O:29])[CH2:25][N:26]=[C:27]=[O:28])[CH3:22]>C(Cl)Cl>[CH2:21]([O:23][C:24](=[O:29])[CH2:25][NH:26][C:27]([C:5]1[C:6](=[O:12])[S:7][C:8]2[C:3]([C:4]=1[OH:13])=[C:2]([F:1])[CH:11]=[CH:10][CH:9]=2)=[O:28])[CH3:22]
Reactant: O=c1cc(O)c2c(F)cccc2s1
Reactant: CCOC(=O)CN=C=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCOC(=O)CNC(=O)c1c(O)c2c(F)cccc2sc1=O
Temperature: 120 °C
Reaction time: 3 h

Procedure:
5-Fluoro-4-hydroxy-thiochromen-2-one (500 mg, 2.55 mmol) was placed in a CEM Microwave vessel and suspended in anhydrous DCM (5 mL.) Triethylamine (710 uL, 5.1 mmol) and isocyanato-acetic acid ethyl ester (572 uL, 5.1 mmol) were added in one portion and the reaction heated to 120° C. in a CEM Discovery Microwave system. After three hours, the reaction was cooled diluted with 10 volumes of dichloromethane, washed with an equal volume of 1N HCl and dried over magnesium sulfate to provide the title compound which was used in the next step without further purification.
Reaction SMILES: [F:1][C:2]([F:9])([F:8])[C:3]([F:7])=[C:4]([F:6])[F:5].[H][H]>>[F:1][C:2]([F:9])([F:8])[CH:3]([F:7])[CH:4]([F:6])[F:5]
Reactant: FC(F)=C(F)C(F)(F)F
Reactant: [H][H]
Product: FC(F)C(F)C(F)(F)F

Procedure:
According to a particularly preferred embodiment (FIG. 1) of the invention, (i) hexafluoropropylene (1) is reacted continuously with hydrogen (2) in the gas phase in a superstoichiometric amount, in an adiabatic reactor (100), in the presence of a catalyst, to give 1,1,1,2,3,3-hexafluoropropane, and a portion (13) of the gaseous output stream resulting from this reaction is recycled; (ii) the nonrecycled part (3) of the output stream resulting from stage (i), comprising 1,1,1,2,3,3-hexafluoropropane, is reacted with potassium hydroxide (4) present in an aqueous reaction medium (200), in an amount of between 20 and 75% by weight and preferably of between 55 and 70% by weight, with respect to the weight of the water and KOH mixture of the reaction medium, maintained at a temperature of between 80 and 180° C., preferably of between 145 and 165° C., to give 1,2,3,3,3-pentafluoro-1-propene and potassium fluoride; (iii) the 1,2,3,3,3-pentafluoro-1-propene (6) obtained in stage (ii) is reacted with hydrogen (2) in the gas phase in a superstoichiometric amount, in an adiabatic reactor (300), in the presence of a catalyst, to give 1,1,1,2,3-penta-fluoropropane and a portion (14) of the gaseous output stream resulting from this reaction is recycled; (iv) the nonrecycled portion (7) of the output stream resulting from stage (iii), comprising 1,1,1,2,3-pentafluoropropane, is subjected to a purification stage (400) in order to remove impurities (8) and thus to obtain 1,1,1,2,3-pentafluoropropane, with a purity preferably of greater than 98% by weight; (v) the 1,1,1,2,3-pentafluoropropane obtained after the purification of stage (iv) is reacted with potassium hydroxide (4) present in an aqueous reaction medium (500), in an amount of between 20 and 75% by weight and preferably of between 55 and 70% by weight, with respect to the weight of the water and KOH mixture of the reaction medium, maintained at a temperature of between 80 and 180° C., preferably of between 145 and 165° C., to give 2,3,3,3-tetrafluoro-1-propene and potassium fluoride; and (vi) the gas stream (9) resulting from the dehydrofluorination stage (v), comprising HFO-1234yf, the unreacted HFC-245eb and the by products, is subjected to a purification stage (600) in order to obtain HFO-1234yf (12) having a purity of greater than 99.5% by weight, preferably of greater than 99.8% by weight. The light by products (10) separated from HFO-1234yf can be subjected to a treatment and the unreacted HFC-245eb (11) can be recycled in (500).
Reaction SMILES: [NH:1]([C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])[CH2:2][CH2:3][C:4]([OH:6])=O.[NH2:17][C@H:18]([C:25]([O:27][CH3:28])=[O:26])[CH2:19][C:20]1[N:24]=[CH:23][NH:22][CH:21]=1.Cl.[N-]=[N+]=[N-].C1(OP(=O)(O)OC2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.C(N(CC)CC)C>[NH:1]([C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])[CH2:2][CH2:3][C:4]([NH:17][C@H:18]([C:25]([O:27][CH3:28])=[O:26])[CH2:19][C:20]1[N:24]=[CH:23][NH:22][CH:21]=1)=[O:6]
Reactant: O=C(O)CCNC(=O)OCc1ccccc1
Reactant: COC(=O)[C@@H](N)Cc1c[nH]cn1
Agent: Cl
Agent: O=P(O)(Oc1ccccc1)Oc1ccccc1
Agent: [N-]=[N+]=[N-]
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COC(=O)[C@H](Cc1c[nH]cn1)NC(=O)CCNC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A solution of 12.3 g of Z-β-Ala-OH and 16.0 g of H-His-OCH3 ×2 HCl in 300 ml of DMF is cooled to 0° and there are added dropwise thereto first a solution of 22.75 g of phosphoric acid diphenyl ester azide in 110 ml of DMF and then a solution of 30.7 ml of triethylamine in 110 ml of DMF. The suspension so obtained is stirred for 2 days at room temperature and then concentrated to an oily suspension in a high vacuum. The residue is taken up in ethyl acetate, washed with sodium bicarbonate and brine, dried and concentrated by evaporation. The crude product is separated by flash chromatography (1.6 kg of silica gel [type 60, Merck], 40-63 μm, 0.4 bar, fractions of 400 ml, eluant: CH2Cl2 /MeOH[13:2]). By concentration by evaporation of the appropriate fractions, Z-β-Ala-His-OCH3 is obtained as a slightly yellowish foam; Rf (L)=0.69.
Reaction SMILES: [C:1]1([CH2:15][OH:16])[C:14]2[CH2:13][CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.[Cl:23][C:24]([Cl:34])=[CH:25][C@@H:26]1[C@H:28]([C:29](Cl)=[O:30])[C:27]1([CH3:33])[CH3:32]>C1C=CC=CC=1>[Cl:23][C:24]([Cl:34])=[CH:25][C@@H:26]1[C@H:28]([C:29]([O:16][CH2:15][C:1]2[C:14]3[CH2:13][CH2:12][C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[C:5]=3[CH:4]=[CH:3][CH:2]=2)=[O:30])[C:27]1([CH3:32])[CH3:33]
Reactant: OCc1cccc2c1CCc1ccccc1-2
Reactant: CC1(C)[C@H](C=C(Cl)Cl)[C@@H]1C(=O)Cl
Solvent: c1ccccc1
Solvent: c1ccncc1
Product: CC1(C)[C@H](C=C(Cl)Cl)[C@@H]1C(=O)OCc1cccc2c1CCc1ccccc1-2
Temperature: 25 °C
Reaction time: 60 h

Procedure:
A mixture of 9,10-dihydrophenanthrene-1-methanol (0.5 gram, 0.0024 mole) and pyridine (1 gram, 0.013 mole) in benzene (25 ml) was added to a stirred solution of cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarbonyl chloride (0.7 gram, 0.0031 mole) in benzene (25 ml). The mixture was stirred at room temperature for 2.5 days, then partitioned between water (80 ml) and diethyl ether (50 ml). The organic phase was separated and washed consecutively with water, 10% aqueous sodium carbonate and water. The organic phase was then dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated to give a yellow oil. The oil was purified by chromatography on silica gel to give (9.10-dihydro-1-phenanthryl)methyl cis-3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylate as an oil.
Reaction SMILES: [CH2:1]1[O:3][C@H:2]1[CH2:4]Cl.[CH:6]1([C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>C(#N)C>[CH:6]1([C:12]2[CH:13]=[CH:14][C:15]([O:18][CH2:4][CH:2]3[CH2:1][O:3]3)=[CH:16][CH:17]=2)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1
Reactant: ClC[C@H]1CO1
Reactant: Oc1ccc(C2CCCCC2)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CC#N
Product: c1cc(C2CCCCC2)ccc1OCC1CO1

Procedure:
To a mixture of R-epichlorohydrin (9.8 g, 106 mmol) and 4-cyclohexylphenol (3.73 g, 21.2 mmol) in acetonitrile (40 ml) was added cesium carbonate (6.9 g, 21.2 mmol). The mixture was heated at reflux for 3 hours. The reaction mixture was cooled, poured into water (100 mL) and extracted twice with EtOAc. The organic phases were combined and washed with water, brine, dried (Na2SO4), concentrated and dried under high vacuum overnight to give the title compound.
Reaction SMILES: [CH2:1]1[CH:5]2[CH:6]3C=CC([CH:4]2[CH:3]=[CH:2]1)C3.C[SiH:12]([Cl:14])[Cl:13].CCCCCCCCCCCCCCCC>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)CCCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(C)C=CC=CC=1>[CH:5]1([CH2:6][SiH:12]([Cl:14])[Cl:13])[CH2:4][CH2:3][CH:2]=[CH:1]1
Reactant: C[SiH](Cl)Cl
Reactant: C1=CC2C3C=CC(C3)C2C1
Agent: Cl[Pd]Cl
Agent: c1ccc(P(CCCCP(c2ccccc2)c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: CCCCCCCCCCCCCCCC
Product: Cl[SiH](Cl)CC1C=CCC1
Reaction time: 2 h
Yield: 337.4 %

Procedure:
As described in Example 2, 2.85 g (0.0216 mol) of dicyclopentadiene, 3.72 g (0.0323 mol) of methyldichlorosilane, 0.040 g (0.000226 mol) of palladium dichloride, 0.19 g (0.000451 mol) of 1,4-bis(diphenylphosphino)butane and 4 mL of toluene and 2 mL of hexadecane were placed in a reactor. The reactor was sealed and the reaction was performed at 180° C. for 2 hours. Products were subject to simple vacuum distillation, thereby providing a mixture (13.2 g) of (2-cyclopentenyl)methyldichlorosilane (4.1 g, 70%), other unreacted reactants, toluene, hexadecane, and unidentified compounds.
Reaction SMILES: C[O:2][C:3](=[O:29])[C@@H:4]([NH2:28])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][CH2:14][C:15]2[N:16]=[C:17]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[O:18][C:19]=2[CH3:20])=[C:8]([Br:27])[CH:7]=1.[CH3:30][C:31]1[CH:41]=[CH:40][C:34]([CH:35]=[CH:36][C:37](O)=[O:38])=[CH:33][CH:32]=1>>[Br:27][C:8]1[CH:7]=[C:6]([CH2:5][C@H:4]([NH:28][C:37](=[O:38])[CH:36]=[CH:35][C:34]2[CH:40]=[CH:41][C:31]([CH3:30])=[CH:32][CH:33]=2)[C:3]([OH:2])=[O:29])[CH:11]=[CH:10][C:9]=1[O:12][CH2:13][CH2:14][C:15]1[N:16]=[C:17]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:18][C:19]=1[CH3:20]
Reactant: COC(=O)[C@@H](N)Cc1ccc(OCCc2nc(-c3ccccc3)oc2C)c(Br)c1
Reactant: Cc1ccc(C=CC(=O)O)cc1
Product: Cc1ccc(C=CC(=O)N[C@@H](Cc2ccc(OCCc3nc(-c4ccccc4)oc3C)c(Br)c2)C(=O)O)cc1
Yield: 24 %

Procedure:
Following the procedures described in Example 1, Intermediate 3B was used in place of Intermediate 3A, and 4-methylcinnamic acid was used in place of cinnamic acid to give (2S)-3-{3-bromo-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-phenyl}-2-(3-p-tolylacryloylamino)-propanoic acid as a white solid with the yield of 24% and mp of 243˜245° C.
Reaction SMILES: [C:1]([N:8]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[C:9]1[CH:14]=[N:13][CH:12]=[C:11](B2OC(C)(C)C(C)(C)O2)[N:10]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Br[C:32]1[N:33]=[C:34]([N:41]([C:49]2[CH:54]=[CH:53][C:52]([N:55]3[CH2:60][CH2:59][N:58]([CH:61]4[CH2:64][O:63][CH2:62]4)[CH2:57][CH2:56]3)=[CH:51][CH:50]=2)[C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[C:35]2[N:36]([CH:38]=[CH:39][N:40]=2)[CH:37]=1.C([O-])([O-])=O.[Na+].[Na+].O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:27]([O:26][C:24]([N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:7])[CH3:6])=[O:2])[C:9]1[N:10]=[C:11]([C:32]2[N:33]=[C:34]([N:41]([C:49]3[CH:54]=[CH:53][C:52]([N:55]4[CH2:56][CH2:57][N:58]([CH:61]5[CH2:62][O:63][CH2:64]5)[CH2:59][CH2:60]4)=[CH:51][CH:50]=3)[C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45])[C:35]3[N:36]([CH:38]=[CH:39][N:40]=3)[CH:37]=2)[CH:12]=[N:13][CH:14]=1)=[O:25])([CH3:29])([CH3:28])[CH3:30]
Reactant: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)c1cncc(B2OC(C)(C)C(C)(C)O2)n1
Reactant: CC(C)(C)OC(=O)N(c1ccc(N2CCN(C3COC3)CC2)cc1)c1nc(Br)cn2ccnc12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)c1cncc(-c2cn3ccnc3c(N(C(=O)OC(C)(C)C)c3ccc(N4CCN(C5COC5)CC4)cc3)n2)n1
Temperature: 110 °C
Yield: 90.8 %

Procedure:
The freshly formed N,N-BisBoc 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazin-2-amine XV (2.67 mmol based on 100% conversion, 2.0 equiv based on bromide) was dissolved in 20 Ml of 1,2-dimethoxyethane and to that solution was added tert-butyl (6-bromoimidazo[1,2-a]pyrazin-8-yl)(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)carbamate IV (707 mg, 1.34 mmol, 1.0 equiv), Na2CO3 (283 mg, 2.67 mmol, 2.0 equiv), Pd(PPh3)4 (155 mg, 0.134 mmol, 0.1 equiv) and water (10 mL) and the solution was degassed for 5 min using N2 gas. The reaction was then placed under N2 atmosphere and heated at 110° C. for 90 min. LCMS showed complete consumption of the bromide starting material and the reaction was removed from heat and allowed to cool to RT. The reaction was diluted with 100 mL water and 100 mL 20% MeOH/DCM and the organic layer was recovered, extracted 1× sat. NaHCO3, 1× sat brine and then dried over Na2SO4. The solution was then filtered and concentrated down to an orange-red solid. The sample was then slurried in warm MeOH, sonicated then filtered, washing 2×20 mL with cold MeOH and then the cream-colored solid was dried on hi-vacuum overnight to yield 905 mg of tert-butyl (6-(6-(bis(tert-butoxycarbonyl)amino)pyrazin-2-yl)imidazo[1,2-a]pyrazin-8-yl)(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)carbamate XVI.
Reaction SMILES: [C:1]([C:5]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:6]=1[C:7]1[C:8](=[O:18])[CH2:9][CH2:10][CH2:11][C:12]=1[NH:13]2)([O:3][CH3:4])=[O:2].[F:19][C:20]([F:30])([F:29])[C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[CH2:23]Br>CN(C=O)C.C(OCC)(=O)C>[F:19][C:20]([F:29])([F:30])[C:21]1[CH:28]=[CH:27][CH:26]=[CH:25][C:22]=1[CH2:23][N:13]1[C:12]2[CH2:11][CH2:10][CH2:9][C:8](=[O:18])[C:7]=2[C:6]2[C:14]1=[CH:15][CH:16]=[CH:17][C:5]=2[C:1]([O:3][CH3:4])=[O:2]
Reactant: FC(F)(F)c1ccccc1CBr
Reactant: COC(=O)c1cccc2[nH]c3c(c12)C(=O)CCC3
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)c1cccc2c1c1c(n2Cc2ccccc2C(F)(F)F)CCCC1=O
Reaction time: 0.5 h
Yield: 83.5 %

Procedure:
40% Methanolic Triton B (2.18 mL, 4.8 mM) was slowly added dropwise to a solution of 5-carbomethoxy-1,2-dihydro-9H-carbazol-4(3H)-one (973 mg, 4.0 mM) in 10 mL of DMF at −10° C. After 30 minutes, 2-(trifluoromethyl)benzyl bromide (1.3 g, 5.2 mM) was added and the resultant mixture stirred at room temperature for 23 hours. The mixture was diluted with ethyl acetate, washed five times with H2O, once with saturated brine, dried over anhydrous magnesium sulfate, filtered, concentrated, and dried in vacuo to afford 1.34 g (83%) of the 9-[(2-trifluoromethylphenyl)methyl]-5-carbomethoxy-1,2-dihydrocarbazol-4(3H)-one as a tan solid. 1H NMR (CDCl3) δ7.7 (d, 1H, J=8 Hz), 7.4-7.1 (m, 5H), 6.4 (d, 1H, J=8 Hz), 5.5 (s, 2H), 4.05 (s, 3H), 2.8 (t, 2H, J=6 Hz), 2.6 (t, 2H, J=6 Hz), and 2.2 (m, 2H). IR (KBr, cm−1) 1729 and 1656. MS (ES) m/e 402.