Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Li])(C)(C)C.[C:6]([O:10][C:11](=[O:19])[NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1)([CH3:9])([CH3:8])[CH3:7].CN(C)[CH:22]=[O:23]>C(OCC)C>[C:6]([O:10][C:11](=[O:19])[NH:12][C:13]1[C:18]([CH:22]=[O:23])=[CH:17][CH:16]=[CH:15][N:14]=1)([CH3:9])([CH3:7])[CH3:8]
Reactant: CC(C)(C)OC(=O)Nc1ccccn1
Reactant: CN(C)C=O
Agent: [Li]C(C)(C)C
Solvent: CCOCC
Product: CC(C)(C)OC(=O)Nc1ncccc1C=O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
tert-Butyllithium (1.7 M, 14.5 mL, 24.6 mmol, 2.39 equiv) was added to a solution of pyridin-2-yl-carbamic acid tert-butyl ester (5-1, 2.00 g, 10.3 mmol, 1 equiv) in ethyl ether (100 mL) at −78° C., and the resulting mixture was warmed to 0° C. and stirred for 1 h. N,N-Dimethylformamide (8.00 mL, 103 mmol, 10.0 equiv) was added with rapid stirring. The mixture was stirred at 0° C. for 10 min, then partitioned between half-saturated aqueous ammonium chloride solution (100 mL). The aqueous layer was further extracted with ethyl acetate (100 mL), and the combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (40% ethyl acetate in hexanes) to afford (3-formyl-pyridin-2-yl)-carbamic acid tert-butyl ester (5-2) as a white solid.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]2[N:8]([N:10]=[C:11]([C:13]3[CH:30]=[CH:29][C:16]([O:17][CH2:18][C@@H:19]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH3:20])=[CH:15][CH:14]=3)[CH:12]=2)[CH:9]=1)[CH3:2].[F:31][B-](F)(F)F.F[B-](F)(F)F.F[N+]1C=CC=CC=1C1C=CC=C[N+]=1F.C(=O)([O-])O.[Na+]>C(#N)C>[CH2:1]([O:3][C:4]1[CH:5]=[CH:6][C:7]2[N:8]([N:10]=[C:11]([C:13]3[CH:30]=[CH:29][C:16]([O:17][CH2:18][C@@H:19]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:27])[CH3:26])[CH3:20])=[CH:15][CH:14]=3)[C:12]=2[F:31])[CH:9]=1)[CH3:2]
Reactant: CCOc1ccc2cc(-c3ccc(OC[C@H](C)NC(=O)OC(C)(C)C)cc3)nn2c1
Reactant: F[B-](F)(F)F
Agent: F[n+]1ccccc1-c1cccc[n+]1F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Product: CCOc1ccc2c(F)c(-c3ccc(OC[C@H](C)NC(=O)OC(C)(C)C)cc3)nn2c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 30.9 %

Procedure:
A mixture of tert-butyl {(1S)-2-[4-(6-ethoxypyrazolo[1,5-a]pyridin-2-yl)phenoxy]-1-methylethyl}carbamate (400 mg), 1,1′-difluoro-2,2′-bipyridinium bis(tetrafluoroborate) (358 mg) and acetonitrile (3 mL) was stirred at room temperature for 3 hr. The reaction mixture was neutralized with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The separated organic layer was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound as colorless crystals (129 mg).
Reaction SMILES: Cl.[NH:2]1[CH2:5][CH:4]([CH2:6][S:7]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH2:3]1.Br[CH2:19][C:20]([C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1)=[O:21]>>[F:28][C:25]1[CH:26]=[CH:27][C:22]([C:20](=[O:21])[CH2:19][N:2]2[CH2:5][CH:4]([CH2:6][S:7]([C:10]3[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][CH:11]=3)(=[O:9])=[O:8])[CH2:3]2)=[CH:23][CH:24]=1
Reactant: O=C(CBr)c1ccc(F)cc1
Reactant: N#Cc1ccc(S(=O)(=O)CC2CNC2)cc1
Agent: Cl
Product: N#Cc1ccc(S(=O)(=O)CC2CN(CC(=O)c3ccc(F)cc3)C2)cc1
Yield: 29 %

Procedure:
Following the procedure of Example 2, 4-[(azetidin-3-ylmethyl)sulfonyl]benzonitrile hydrochloride (75 mg, 0.27 mmol) was reacted with 2-bromo-1-(4-fluorophenyl)ethanone. Crude product was purified on a 10 g bond elute silica cartridge using the personal flash master eluting with 0.5% MeOH/DCM to 2% MeOH/DCM to give the freebase as a pale yellow gum (30 mg, 29%). The freebase was dissolved in 3:1 ether/MeOH (5 ml) and 1.0M hydrogen chloride in ether (89μl) was added. The side of the flask was etched and the salt precipitated and was isolated by filtration and dried under vacuum to give the title compound as a white solid (20 mg). 1H NMR (500 MHz, CDCl3) δ 3.05–3.13 (1H, m), 3.90–3.96 (2H, m), 4.03–4.12 (2H, m), 4.23–4.30 (2H, m), 5.06 (2H, s), 7.44 (2H, t, J=8.8 Hz), 8.01 (2H, dd, J=5.4 & 8.8 Hz), 8.09 (2H, d, J=8.6 Hz), 8.21 (2H, d, J=8.6 Hz), 10.62 (1H, s). m/z (ES+) 373 (M+H)+.
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[Br:12][C:13]1[C:22]([O:23][CH3:24])=[C:21]2[C:16]([C:17](=[O:35])[C:18]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:19]([S:28][CH3:29])[N:20]2[CH:25]2[CH2:27][CH2:26]2)=[CH:15][CH:14]=1>C(Cl)Cl>[Br:12][C:13]1[C:22]([O:23][CH3:24])=[C:21]2[C:16]([C:17](=[O:35])[C:18]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:19]([S:28]([CH3:29])=[O:6])[N:20]2[CH:25]2[CH2:26][CH2:27]2)=[CH:15][CH:14]=1
Reactant: CCOC(=O)c1c(SC)n(C2CC2)c2c(OC)c(Br)ccc2c1=O
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CCOC(=O)c1c(S(C)=O)n(C2CC2)c2c(OC)c(Br)ccc2c1=O
Reaction time: 1 h
Yield: 55.7 %

Procedure:
m-Chloroperoxybenzoic acid (≦77%, 273.5 mg, 1.22 mmol) is added in one portion to a solution of crude ethyl 15 (from above ˜1.22 mmol) in methylene chloride (5.0 mL) at room temperature. The reaction mixture is stirred for 1 h, diluted with methylene chloride (10 mL), and washed with a saturated aqueous solution of sodium bicarbonate (25 mL). The organic layer is dried over magnesium sulfate and evaporated under reduced pressure to give the crude product. This material is purified by flash column chromatography (eluting with ethyl acetate; Rf 0.37) to give 290.9 mg of pure ethyl 16 as a white solid. 1H NMR (CDCl3): δ 0.54 (m, 1H, c-Pr CH2 (A)), 0.93 (m, 1H, c-Pr CH2 (B)), 1.12 (m, 1H, c-Pr CH2 (A)), 1.28 (m, 1H, c-Pr CH2 (B)), 1.38 (t, J=7.0 Hz, 3H, CO2CH2CH3), 3.26 (s, 3H, S(O)CH3), 3.83 (s, 3H, OCH3), 3.92 (m, 1H, c-Pr CH), 4.40 (m, 2H, overlapping CO2CHHCH3), 7.58 (d, J=8.5 Hz, 1H, aromatic H-6), 7.87 (d, J=8.5 Hz, 1H, aromatic H-5). 13C{1H} NMR (CDCl3): δ 10.8 (br, c-Pr CH2 (A)), 13.9 (br, c-Pr CH2 (B)), 14.1 (CO2CH2CH3), 35.1 (c-Pr CH), 41.4 (S(O)—CH3), 61.1 (OCH3), 62.1 (CO2CH2CH3), 118.9 (C-3), 122.8 (CH, C-5), 123.9 (C—Br, C-7), 129.5 (C-4a), 130.0 (CH, C-6), 138.2 (C-8a), 148.3 (C—OCH3, C-8), 164.0 (CO2CH2CH3), 164.1 (br, C—S(O)—CH3, C-2), 174.6 (C═O, C-4). LCMS m/z calcd for C17H1879BrNO5S ([M]+) 427. Found 428 ([M+H]+). HRMS m/z calcd for C17H1879BrNNaO5S 449.9987 ([M+Na]+). Found 449.9977.
Reaction SMILES: [N:1]1[CH:2]=[CH:3][N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.[Cl-].[Al+3].[Cl-].[Cl-].[C:14](OC(=O)C)(=[O:16])[CH3:15].[OH-].[Na+]>C(Cl)(Cl)Cl>[N:1]1[CH:2]=[C:3]([C:14](=[O:16])[CH3:15])[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12
Reactant: CC(=O)OC(C)=O
Reactant: c1ccn2ccnc2c1
Agent: [Al+3]
Agent: [Cl-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CC(=O)c1cnc2ccccn12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
25 g of imidazo[1,2-a]pyridine was dissolved in 350 mL of chloroform, and 56.4 g of aluminum chloride was added under an ice-cold condition over 30 minutes. The mixture was stirred overnight at room temperature, and then heated up to the temperature of 50° C. 16 mL of acetic anhydride was added and the mixture was stirred at 50° C. for 90 minutes. After cooling the reaction solution back to room temperature, ice water was added, and a 3N aqueous solution of sodium hydroxide was further added until the mixture becomes basic. The insolubles were separated by filtration through celite, the filtrate was extracted with ethyl acetate, and the organic layer was washed with saturated brine. The layer was dried over anhydrous sodium sulfate and then filtered, and the filtrate was concentrated to obtain 1-imidazo[1,2-a]pyridine-3-ylethanone [1-1] as a brown oily product. The obtained Compound [1-1] was used in the subsequent reaction without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[Cl:10])[CH2:5]Br.[C:11]([O:14][C:15]1[C:23]([O:24][CH3:25])=[CH:22][CH:21]=[C:20]2[C:16]=1[CH:17]=[C:18]([C:26]([O:28][CH3:29])=[O:27])[NH:19]2)(=[O:13])[CH3:12].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[C:11]([O:14][C:15]1[C:23]([O:24][CH3:25])=[CH:22][CH:21]=[C:20]2[C:16]=1[CH:17]=[C:18]([C:26]([O:28][CH3:29])=[O:27])[N:19]2[CH2:5][C:4]1[CH:7]=[CH:8][C:9]([Cl:10])=[C:2]([Cl:1])[CH:3]=1)(=[O:13])[CH3:12]
Reactant: Clc1ccc(CBr)cc1Cl
Reactant: COC(=O)c1cc2c(OC(C)=O)c(OC)ccc2[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COC(=O)c1cc2c(OC(C)=O)c(OC)ccc2n1Cc1ccc(Cl)c(Cl)c1
Temperature: 80 °C

Procedure:
3,4-Dichlorobenzyl bromide (1.02 g) was added to a stirred solution of methyl 4-acetoxy-5-methoxyindole-2-carboxylate (0.8 g) and potassium carbonate (0.97 g) in acetonitrile (30 ml) under an atmosphere of argon. The reaction was heated at 80° C. for 16 hours, then concentrated in vacuo and the residue partitioned between ethyl acetate and water.
Reaction SMILES: [C:1]1([C:7]2[C:15]([CH2:16][C:17](=S)[C:18]([OH:20])=[O:19])=[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][N:9]3[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[NH2:23][OH:24].[OH-].[K+].C(O)C>O>[C:1]1([C:7]2[C:15]([CH2:16][C:17](=[N:23][OH:24])[C:18]([OH:20])=[O:19])=[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][N:9]3[N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NO
Reactant: O=C(O)C(=S)Cc1c(-c2ccccc2)nn2ccccc12
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)C(Cc1c(-c2ccccc2)nn2ccccc12)=NO
Yield: 69.8 %

Procedure:
A mixture of 3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-2-thioxopropionic acid (3.74 g), hydroxylamine hydrochloride (2.63 g), 85% potassium hydroxide (2.50 g) and 80% aqueous ethanol (22.4 ml) was refluxed for 3 hours. After cooling, to the reaction mixture was added water (40 ml) and the resulting precipitates were filtered off. The filtrate was washed with methylene chloride (20 ml) twice, acidified with 10% aqueous hydrochloric acid (pH ≈2), and extracted with ethyl acetate (20 ml) twice. The organic layer was washed with water (10 ml) and a saturated aqueous solution of sodium chloride and dried over magnesium sulfate. The solvent was removed to give 3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)-2-hydroxyiminopropionic acid (2.60 g).
Reaction SMILES: FC1C=CC=C(F)C=1[C:9]1[CH:10]=[C:11]2[C:15]3=[C:16]([CH2:18][NH:19][CH2:20][CH2:21][N:14]3[C@H:13]3[CH2:22][CH2:23][NH:24][CH2:25][C@@H:12]23)[CH:17]=1.[Cl:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1B(O)O.[OH-].[Ba+2].[OH-]>COCCOC.C(OCC)(=O)C.O.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>[Cl:26][C:27]1[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=1[C:9]1[CH:10]=[C:11]2[C:15]3=[C:16]([CH2:18][NH:19][CH2:20][CH2:21][N:14]3[C@H:13]3[CH2:22][CH2:23][NH:24][CH2:25][C@@H:12]23)[CH:17]=1
Reactant: Fc1cccc(F)c1-c1cc2c3c(c1)[C@@H]1CNCC[C@@H]1N3CCNC2
Reactant: OB(O)c1ccc(Cl)cc1Cl
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Ba+2]
Agent: [OH-]
Solvent: O
Solvent: CCOC(C)=O
Solvent: COCCOC
Product: Clc1ccc(-c2cc3c4c(c2)[C@@H]2CNCC[C@@H]2N4CCNC3)c(Cl)c1
Temperature: 90 °C
Reaction time: 1 h

Procedure:
tert-butyl (±)-cis-bromo-4-oxo-1,2,3,4,7b,10,11,11a-octahydro[1,4]diazepino[6,7,1-hi]pyrido[4,3-b]indol-9(8H)-carboxylate from EXAMPLE 70, Part E (150 mg, 0.356 mmol), 2,4-dichlorophenylboronic acid (82 mg, 0.430 mmol) and barium hydroxide (170 mg, 0.540 mmol) were dissolved in DME (7 mL) and water (4 mL), and degassed for 10 minutes under nitrogen. Tetrakis (triphenylphosphine)palladium (O) (10 mg, 0.007 mmol) was added and the reaction was heated to 90° C. for 13 h. The reaction was cooled to room temperature and diluted with ethyl acetate (20 mL) and water (20 mL). The organic layer was separated and dried over magnesium sulfate, filtered and concentrated under reduced pressure to give an oil. The oil was purified by silica gel column chromatography (13% ethyl acetate, hexanes). Fractions were collected, concentrated to a solid, then dissolved in 20% TFA/CHCl3 and stirred for 1 hour. The reaction solution was cooled to 0° C. in an ice bath, and basified to pH=10 with concentrated NH4OH. This was extracted with CHCl3 (3×15 ml), organics collected, dried over MgSO4 and concentrated under reduced pressure to give to give the title compound. 1H NMR(CDCl3, 300 MHz): δ 7.52 (d, 1H, J=1.8 Hz), 7.44 (d, 1H, J=1.8 Hz), 7.26-7.20 (m, 2H), 6.45 (s, 1H), 4.34 (t, 2H, J=9.2 Hz), 4.14-4.06 (m, 2H), 3.18-2.95 (m, 3H), 2.88-2.75 (m, 3H), 2.14 (s-br, 1H), 1.96-1.79 (m, 2H) ppm.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]([Cl:11])[C:5]([C:6]([NH2:8])=[O:7])=[C:4]([N+:12]([O-])=O)[C:3]=1[OH:15].O.[Sn](Cl)Cl>>[NH2:12][C:4]1[C:3]([OH:15])=[C:2]([Cl:1])[CH:10]=[C:9]([Cl:11])[C:5]=1[C:6]([NH2:8])=[O:7]
Reactant: NC(=O)c1c(Cl)cc(Cl)c(O)c1[N+](=O)[O-]
Agent: Cl[Sn]Cl
Solvent: O
Product: NC(=O)c1c(Cl)cc(Cl)c(O)c1N

Procedure:
Reduction of 4,6-dichloro-3-hydroxy-2-nitrobenzamide with tin (II) chloride hydrate according to the conditions as described in Step B gave 2-amino-4,6-dichloro-3-hydroxybenzamide as a beige solid (2.5 g, 62% (2 steps)).—1H NMR (CD3OD): δ 6.69 (s, 1H).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([C:10]([OH:12])=[O:11])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[OH-].[K+].[I:15]I.S(=O)(=O)(O)[O-].[Na+]>CN(C=O)C>[I:15][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[C:6]([C:10]([OH:12])=[O:11])[CH:5]=2)[NH:1][CH:2]=1
Reactant: II
Reactant: O=C(O)c1ccc2[nH]ccc2c1
Agent: O=S(=O)([O-])O
Agent: [K+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(O)c1ccc2[nH]cc(I)c2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 89.8 %

Procedure:
To a solution of 1H-Indole-5-carboxylic acid (5 g, 31.05 mmol) in DMF (50 mL) was added KOH (5 g, 93.15 mmol) and I2 (15.7 g, 62.11 mmol). The reaction mixture was stirred at RT for 2 h and added 10% aqueous sodium bisulfate solution (25 mL). The resulting precipitate was collected by filtration, washed with water and dried under vacuum to obtain the title compound (8.0 g, 91%) as a brown solid. MS (ESI, pos. ion) m/z: 285.9 (M−1).
Reaction SMILES: CO[C:3]([C:5]1[S:9][C:8](/[CH:10]=[CH:11]/[C:12]2[C:13]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:14][O:15][C:16]=2[CH3:17])=[N:7][C:6]=1[CH3:24])=[O:4].[CH2:25]([CH2:27][NH2:28])[OH:26]>C1(C)C=CC=CC=1.[Cl-].[Na+].O>[OH:26][CH2:25][CH2:27][NH:28][C:3]([C:5]1[S:9][C:8](/[CH:10]=[CH:11]/[C:12]2[C:13]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[N:14][O:15][C:16]=2[CH3:17])=[N:7][C:6]=1[CH3:24])=[O:4]
Reactant: COC(=O)c1sc(/C=C/c2c(-c3ccccc3)noc2C)nc1C
Reactant: NCCO
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: Cc1nc(/C=C/c2c(-c3ccccc3)noc2C)sc1C(=O)NCCO
Yield: 61.9 %

Procedure:
To a stirred solution of 4-methyl-2-[(E)-2-(5-methyl-3-phenyl-isoxazol-4-yl)-vinyl]-thiazole-5-carboxylic acid methyl ester (70 mg, 0.21 mmol) in toluene (0.5 mL) was added ethanolamine (15 mg, 0.25 mmol) and TBD (18 mg, 0.13 mmol). After 24 h the reaction mixture was diluted with brine and extracted with ethyl acetate. The combined extracts were dried, filtered and concentrated in vacuo, then purified by chromatography (silica, 0 to 10% methanol in dichloromethane) to give the title compound (48 mg, 60%) as a pale yellow oil. MS: m/e=370.1 [M+H]+.
Reaction SMILES: Cl[C:2]1[C:3]2[N:4]([C:12]([CH3:15])=[N:13][N:14]=2)[C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.Cl[C:17]1[C:18]2[N:19](C=NN=2)[C:20]2C(N=1)=CC=C[CH:21]=2.C(NCC)C.C(NCCC)CC>>[CH2:18]([N:19]([CH2:20][CH3:21])[C:2]1[C:3]2[N:4]([C:12]([CH3:15])=[N:13][N:14]=2)[C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2)[CH3:17]
Reactant: Cc1nnc2c(Cl)nc3ccccc3n12
Reactant: Clc1nc2ccccc2n2cnnc12
Solvent: CCCNCCC
Solvent: CCNCC
Product: CCN(CC)c1nc2ccccc2n2c(C)nnc12
Yield: 54 %

Procedure:
This compound was prepared by the method of Example 11, utilizing 4-chloro-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline (the product of Example 3) as starting material in place of 4-chloro-[1,2,4]triazolo[4,3-a]quinoxaline (the product of Example 2) and diethylamine as reagent in place of di-n-propylamine. The crude product obtained was recrystallized from chloroform and then from cyclohexane to afford 7.2 g. (54% yield) of pure 4-diethylamino-1-methyl-[1,2,4]triazolo[4,3-a]quinoxaline, m.p. 123°-125° C.
Reaction SMILES: [BH4-].[Na+].[CH2:3]([O:10][C:11]([NH:13][C@@H:14]([CH2:19][NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:15](OC)=[O:16])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl>CO>[CH2:3]([O:10][C:11]([NH:13][C@@H:14]([CH2:19][NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:15][OH:16])=[O:12])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: COC(=O)[C@H](CNC(=O)OC(C)(C)C)NC(=O)OCc1ccccc1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)OC(=O)NC[C@@H](CO)NC(=O)OCc1ccccc1
Temperature: 25 °C
Yield: 87.7 %

Procedure:
Sodium borohydride (251 mg) was added to a solution of methyl (S)-2-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)propionate (1.17 g) in methanol (10 mL) at 0° C. The mixture was stirred for an hour at the same temperature and then for an hour at ambient temperature. After addition of 3.6% hydrochloric acid, the mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and an aqueous saturated sodium bicarbonate solution. The organic layer was washed with brine, dried over magnesium sulfate and concentrated in vacuo. The residual crystals were suspended in hot diisopropyl ether and cooled to ambient temperature with stirring. The residual crystals were collected by filtration and washed with diisopropyl ether to give (S)-2-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)propanol (945 mg) as white crystals.
Reaction SMILES: Br[C:2]1[S:6][CH:5]=[N:4][C:3]=1[C:7]([O:9][CH3:10])=[O:8].[C:11]1([C:17]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[NH:18])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(Cl)(Cl)Cl.C(OCC)(=O)C>[C:11]1([C:17](=[N:18][C:2]2[S:6][CH:5]=[N:4][C:3]=2[C:7]([O:9][CH3:10])=[O:8])[C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: N=C(c1ccccc1)c1ccccc1
Reactant: COC(=O)c1ncsc1Br
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Solvent: CCOC(C)=O
Product: COC(=O)c1ncsc1N=C(c1ccccc1)c1ccccc1
Temperature: 80 °C
Yield: 84.4 %

Procedure:
A mixture of methyl 5-bromothiazole-4-carboxylate (3.51 g, 15.8 mmol), diphenylmethanimine (4.0 ml, 23.9 mmol), cesium carbonate (10.98 g, 33.7 mmol), Pd2(dba)3-CHCl3 (876 mg, 957 umol), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 1.67 g, 2.89 mmol) in toluene (30 ml) was heated at 80° C. for 18 h. The heterogeneous mixture was directly flash chromatographed with 9:1, 4:1, 7:3, 3:2 and 1:1 hexane:ethyl acetate as the eluant to yield 4.30 g (84% yield) of methyl 5-(diphenylmethyleneamino)thiazole-4-carboxylate as a yellow oil. Retention time (min)=6.41, method [7], MS (ESI) 323.0 (M+H).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([N:12]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[Cl:25])[C:13](=[O:17])[O:14][CH2:15][CH3:16])=[C:4]([N+:26]([O-:28])=[O:27])[CH:3]=1.Cl.[CH3:30][N:31](C)C=O>[C-]#N.[Zn+2].[C-]#N.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>[Cl:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[CH2:18][N:12]([C:5]1[C:6]([C:8]([F:11])([F:10])[F:9])=[CH:7][C:2]([C:30]#[N:31])=[CH:3][C:4]=1[N+:26]([O-:28])=[O:27])[C:13](=[O:17])[O:14][CH2:15][CH3:16]
Reactant: CN(C)C=O
Reactant: CCOC(=O)N(Cc1ccccc1Cl)c1c([N+](=O)[O-])cc(Br)cc1C(F)(F)F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Agent: [C-]#N
Product: CCOC(=O)N(Cc1ccccc1Cl)c1c([N+](=O)[O-])cc(C#N)cc1C(F)(F)F
Temperature: 60 °C
Reaction time: 7 h
Yield: 59 %

Procedure:
Ethyl 4-bromo-2-nitro-6-(trifluoromethyl)phenyl(2-chlorobenzyl)carbamate (620.3 mg) was dissolved in N,N-dimethylformamide (30 ml), and to the solution were added zinc cyanide (302.4 mg) and tetrakis(triphenylphosphine)palladium(0) (1.116 g). The mixture was heated at 60° C. and stirred for 7 hours. After allowing to cool, to the reaction mixture was added 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The resultant residue was purified by silica gel column (100 g, hexane:ethyl acetate=3:1) to give the title compound (322.6 mg, 59%).
Reaction SMILES: O1C2C(=CC=CC=2)C=CC1=O.[C:12](O)(=[O:29])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]>>[CH:12](=[O:29])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28]
Reactant: CCCCCCCCCCCCCCCCC(=O)O
Agent: O=c1ccc2ccccc2o1
Product: CCCCCCCCCCCCCCCCC=O
Yield: 21 %

Procedure:
After the reaction, the autoclave was cooled with ice, and the pressure was reduced; subsequently, the reaction mixture was analyzed by FT-NMR using coumarin as an internal standard. The results confirmed that heptadecanoic acid was obtained in a yield of 78%, and heptadecanal was obtained in a yield of 21%.