Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:5]1[C:10]([CH3:11])=[CH:9][C:8](=[O:12])[C:7]([C:13]([NH:15][C:16]2[C:21]([CH2:22][CH3:23])=[CH:20][CH:19]=[CH:18][C:17]=2[CH2:24][CH3:25])=[O:14])=[C:6]1[CH3:26])[CH2:2][CH2:3][CH3:4].[Cl:27]N1C(=O)CCC1=O>C(Cl)(Cl)Cl>[CH2:1]([N:5]1[C:10]([CH3:11])=[C:9]([Cl:27])[C:8](=[O:12])[C:7]([C:13]([NH:15][C:16]2[C:17]([CH2:24][CH3:25])=[CH:18][CH:19]=[CH:20][C:21]=2[CH2:22][CH3:23])=[O:14])=[C:6]1[CH3:26])[CH2:2][CH2:3][CH3:4]
Reactant: O=C1CCC(=O)N1Cl
Reactant: CCCCn1c(C)cc(=O)c(C(=O)Nc2c(CC)cccc2CC)c1C
Solvent: ClC(Cl)Cl
Product: CCCCn1c(C)c(Cl)c(=O)c(C(=O)Nc2c(CC)cccc2CC)c1C

Procedure:
A mixture of 500 mg (1.41 mmol, m.p. 110°-112° C.) of 1-butyl-N-(2,6-diethylphenyl)-1,4-dihydro-2,6-dimethyl-4-oxo-3-pyridinecarboxamide and 188 mg (1.41 mmol) of N-chlorosuccinimide was dissolved in 15 ml of chloroform and refluxed with stirring. To the reaction mixture, 190 mg of N-chloro-succinimide was added in twice, and refluxed for 15.2 hours.
Reaction SMILES: [C:1]12([C:11]3[CH:12]=[C:13]([CH:16]=[CH:17][C:18]=3[O:19][CH3:20])[CH:14]=O)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[NH2:21][C:22]1[CH:33]=[CH:32][C:25]([C:26]([O:28][CH2:29][CH:30]=[CH2:31])=[O:27])=[CH:24][CH:23]=1>>[C:1]12([C:11]3[CH:12]=[C:13]([CH:16]=[CH:17][C:18]=3[O:19][CH3:20])[CH:14]=[N:21][C:22]3[CH:23]=[CH:24][C:25]([C:26]([O:28][CH2:29][CH:30]=[CH2:31])=[O:27])=[CH:32][CH:33]=3)[CH2:2][CH:3]3[CH2:4][CH:5]([CH2:6][CH:7]([CH2:9]3)[CH2:8]1)[CH2:10]2
Reactant: C=CCOC(=O)c1ccc(N)cc1
Reactant: COc1ccc(C=O)cc1C12CC3CC(CC(C3)C1)C2
Product: C=CCOC(=O)c1ccc(N=Cc2ccc(OC)c(C34CC5CC(CC(C5)C3)C4)c2)cc1
Yield: 75.8 %

Procedure:
Starting with 3.4 g (12.6 mmoles) of 3-(1-adamantyl)-4-methoxybenzaldehyde and 2.6 g (14.4 mmoles) of allyl 4-aminobenzoate the synthesis is effected following the procedures described in Example 8. The resulting crude product is recrystallized in ethyl acetate. After filtration and drying, 4.1 g (76%) of the allylic ester whose melting point is 160°-162° C. are obtained.
Reaction SMILES: [Cl:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([CH:7]=[N:8][OH:9])=[CH:5][CH:4]=1.C1C(=O)N([Cl:19])C(=O)C1.Cl.O1CCOCC1>CN(C=O)C>[Cl:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([Cl:19])=[N:8][OH:9])=[CH:5][CH:4]=1
Reactant: O=C1CCC(=O)N1Cl
Reactant: ON=Cc1ccc(CCl)cc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: C1COCCO1
Product: ON=C(Cl)c1ccc(CCl)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 113.9 %

Procedure:
4-(chloromethyl)benzaldehyde oxime 5 (15.8 g, 93.16 mmol) was dissolved in DMF (300 mL). NCS (13.69 g, 102.5 mmol) was added in portions and then HCl in dioxane (100 mL of 4 M, 400.0 mmol) was added slowly, cooling the mixture with an ice water bath to moderate the exotherm, keeping internal temperature below 33° C. The mixture was then stirred at room temperature for 1 hour. The solution was partitioned between EtOAc and water and the organic extract was washed with water and brine (5×200 ml), dried over MgSO4 and concentrated under reduced pressure to give a colourless solid (21.65 g, 95%). 1H NMR (400 MHz, CDCl3) δ 4.63 (2H, s), 7.45 (2H, d, J=8 Hz), 7.86 (2H, d, J=8 Hz), 8.36 (1H, s).
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:12](=[O:13])[CH:11]=[N:10][N:9]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=2)[CH:8]=1)(=O)=O.[C:26]1([N:32]2[C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][CH:34]=[N:33]2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>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.C(O)C>[C:26]1([N:32]2[C:36]([C:7]3[C:12](=[O:13])[CH:11]=[N:10][N:9]([C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=4)[CH:8]=3)=[CH:35][CH:34]=[N:33]2)[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1
Reactant: O=c1cnn(-c2cccc(C(F)(F)F)c2)cc1OS(=O)(=O)C(F)(F)F
Reactant: CC1(C)OB(c2ccnn2-c2ccccc2)OC1(C)C
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: Cc1ccccc1
Solvent: CCO
Solvent: O
Product: O=c1cnn(-c2cccc(C(F)(F)F)c2)cc1-c1ccnn1-c1ccccc1
Temperature: 100 °C
Reaction time: 6 h
Yield: 8.8 %

Procedure:
5-oxo-2-[3-(trifluoromethyl)phenyl]-2,5-dihydropyridazin-4-yl trifluoromethanesulfonate (0.100 g), 1-phenyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.139 g), sodium carbonate (0.109 g) and tetrakis(triphenylphosphine)palladium(0) (0.0298 g) were suspended in a mixed solvent of toluene (2.06 mL), ethanol (0.52 mL) and water (0.52 mL), and the suspension was stirred at 100° C. for 6 hr under an argon atmosphere. The reaction mixture was cooled to room temperature, diluted with water, extracted with ethyl acetate, washed with aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous magnesium sulfate, filtered, concentrated, purified by NH silica gel column chromatography (ethyl acetate/hexane) and recrystallized from ethyl acetate/hexane to give the title compound (0.0087 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6](Cl)=[O:7].[CH2:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH2:22][CH3:23])[CH3:15].[Cl-].[Al+3].[Cl-].[Cl-].COC1C=C(C(C2C=CC(OC)=CC=2)=CC#N)C=CC=1OC>>[CH2:14]([C:16]1[CH:21]=[C:20]([C:6]([C:5]2[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:3]([O:2][CH3:1])[CH:4]=2)=[O:7])[CH:19]=[CH:18][C:17]=1[CH2:22][CH3:23])[CH3:15]
Reactant: COc1ccc(C(=O)Cl)cc1OC
Reactant: CCc1ccccc1CC
Agent: COc1ccc(C(=CC#N)c2ccc(OC)c(OC)c2)cc1
Agent: [Al+3]
Agent: [Cl-]
Product: CCc1ccc(C(=O)c2ccc(OC)c(OC)c2)cc1CC
Yield: 41.1 %

Procedure:
3,4-Dimethoxybenzoyl chloride (4.01 g, 20 mmol), 1,2-diethylbenzene (2.68 g, 20 mmol), and aluminum chloride (2.93 g, 22 mmol) were treated in the same manner as described above for the synthesis of 3-(3,4-dimethoxy-phenyl)-3-(4-methoxy-phenyl)-acrylonitrile. The crude was purified via flash column chromatography (10% EtOAc in hexane gradient to 20% EtOAc in hexane in 40 min.) to give (3,4-diethyl-phenyl)-(3,4-dimethoxy-phenyl)-methanone as an orange oil (2.45 g, 41%). The product was carried over without further purification to the next step.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]([NH:9][N:10]([CH3:15])[C:11]([NH:13][CH3:14])=[S:12])=O)=[CH:3][CH:2]=1.C([O-])(O)=O.[Na+]>>[N:1]1[CH:6]=[CH:5][C:4]([C:7]2[N:13]([CH3:14])[C:11](=[S:12])[N:10]([CH3:15])[N:9]=2)=[CH:3][CH:2]=1
Reactant: CNC(=S)N(C)NC(=O)c1ccncc1
Agent: O=C([O-])O
Agent: [Na+]
Product: Cn1nc(-c2ccncc2)n(C)c1=S

Procedure:
The 1:1 mixture from Example 2 and 1 molar aqueous NaHCO3 (100 ml, 1.00×10-1 mole) were stirred and warmed to reflux. After refluxing for 15 hours the reaction was allowed to cool in an ice bath. The resulting precipitate was collected by filtration and was dried by suction. The desired product was crystallized from ethyl acetate/hexane to yield large colorless plates: 4.1 g (35%), mp 150°-152° C.
Reaction SMILES: C=CC=C.O.C(=O)=[O:7].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:28](O)[CH:29]=[CH:30][CH2:31][CH2:32][CH2:33][CH:34]=[CH2:35]>[Pd].C(CC(=O)C)(=O)C.C(CC(=O)C)(=O)C.CN(C)C=O>[CH2:28]=[CH:29][CH:30]([OH:7])[CH2:31][CH2:32][CH2:33][CH:34]=[CH2:35]
Reactant: O=C=O
Reactant: C=CCCCC=CCO
Agent: [Pd]
Agent: C=CC=C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: O
Solvent: CC(=O)CC(C)=O
Product: C=CCCCC(O)C=C
Yield: 12.4 %

Procedure:
A mixture composed of 0.5 mol of 1,3-butadiene, 1 mol of water, 0.6 mol of carbon dioxide, 0.5 milli-mol of bis(acetylacetone) palladium, 2.0 milli-mol of triphenyl phosphine, and 63 ml of dimethylformamide was placed in an electromagnetic induction rotary type autoclave made of stainless steel having an internal volume of 0.3l, and subjected to reaction for three hours at a temperature of 90° C. Analysis of the resulted liquid reaction product through gas chromatography revealed that 0.153 mol of 2,7-octadien-1-ol, and 0.019 mol of 1,7-octadien-3-ol were produced.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:29])[CH2:9][NH:10][CH:11]([CH3:28])[CH2:12][C:13]2[CH:27]=[CH:26][C:16]3[O:17][C:18]([C:23]([OH:25])=[O:24])([C:20]([OH:22])=[O:21])[O:19][C:15]=3[CH:14]=2)[CH:5]=[CH:6][CH:7]=1.[CH2:30]([O:32][CH2:33][CH2:34]O)[CH3:31].Cl>>[ClH:1].[CH2:16]([O:17][CH2:18][CH2:20][O:24][C:23]([C:18]1([C:20]([O:22][CH2:34][CH2:33][O:32][CH2:30][CH3:31])=[O:21])[O:17][C:16]2[CH:26]=[CH:27][C:13]([CH2:12][CH:11]([NH:10][CH2:9][CH:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[OH:29])[CH3:28])=[CH:14][C:15]=2[O:19]1)=[O:25])[CH3:15]
Reactant: CCOCCO
Reactant: CC(Cc1ccc2c(c1)OC(C(=O)O)(C(=O)O)O2)NCC(O)c1cccc(Cl)c1
Agent: Cl
Product: CCOCCOC(=O)C1(C(=O)OCCOCC)Oc2ccc(CC(C)NCC(O)c3cccc(Cl)c3)cc2O1

Procedure:
The title compound was prepared from 5-{2-[2-(3-chloro-phenyl)-2-hydroxy-ethylamino]-propyl}-benzo[1,3]dioxole-2,2-dicarboxylic acid and 2-ethoxyethanol according to the procedure of Example 1 as an oily off-white gummy solid; 1H NMR (300 MHz, CDCl3): δ 1.10-1.20 (t overlaps with d, J=6.9 Hz, 9H), 1.31-1.41 (brm, 2H), 2.75-2.90 (brm, 1H), 3.10-3.30 (brm, 2H), 3.50 (brq, J=6.9 Hz, 4H), 3.62-3.71 (brm, 4H), 4.37-4.47 (brm, 4H), 5.30-5.70 (brm, 2H), 6.70-6.90 (brm, 4H), 7.19-7.50 (brm, 3H), 8.50-8.85 (brs, 1H), 9.90-10.30 (brs, 1H); MS (ES) m/z (relative intensity): 566 (M+ -HCl, (60).
Reaction SMILES: [CH2:1]1[C@H:5]2[C:6](=[O:16])[NH:7][C:8]3[CH:15]=[CH:14][CH:13]=[CH:12][C:9]=3[C:10](=[O:11])[N:4]2[CH2:3][CH2:2]1.[N+:17]([O-])([OH:19])=[O:18]>>[N+:17]([C:13]1[CH:14]=[CH:15][C:8]2[NH:7][C:6](=[O:16])[C@@H:5]3[CH2:1][CH2:2][CH2:3][N:4]3[C:10](=[O:11])[C:9]=2[CH:12]=1)([O-:19])=[O:18]
Reactant: O=[N+]([O-])O
Reactant: O=C1Nc2ccccc2C(=O)N2CCC[C@@H]12
Product: O=C1Nc2ccc([N+](=O)[O-])cc2C(=O)N2CCC[C@@H]12
Temperature: 25 °C
Reaction time: 18 h

Procedure:
130 ml of 89 percent nitric acid are treated portionwise at room temperature over a period of 1.5 hours with 43.0 (199 mmol) of (S)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H)-dione. The mixture is stirred at room temperature for 18 hours and poured into 1.5 l of ice-water. The precipitated material is filtered off under suction, washed with a large amount of water and dried at 80° in vacuo. There is obtained (S)-(+)-1,2,3,11a-tetrahydro-7-nitro-5H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H)-dione of melting point 259°-261°.
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[C@@H:7]2[O:8][C@@H:6]2[C:5]2[CH:9]=[C:10]([C:13]#[N:14])[CH:11]=[CH:12][C:4]=2[O:3]1.C(C1C=C[C:21]2[O:26][C:25](C)(C)[C@H:24](O)[C@@H:23]([N:30](CC(OCC)=O)[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:22]=2C=1)#N>CO>[O:26]1[CH:21]=[CH:22][C:24]([CH2:23][N:30]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[C@H:6]2[C:5]3[CH:9]=[C:10]([C:13]#[N:14])[CH:11]=[CH:12][C:4]=3[O:3][C:2]([CH3:15])([CH3:1])[C@@H:7]2[OH:8])=[CH:25]1
Reactant: CCOC(=O)CN(c1ccccc1)[C@H]1c2cc(C#N)ccc2OC(C)(C)[C@@H]1O
Reactant: CC1(C)Oc2ccc(C#N)cc2[C@H]2O[C@H]21
Solvent: CO
Product: CC1(C)Oc2ccc(C#N)cc2[C@H](N(Cc2ccoc2)c2ccccc2)[C@H]1O

Procedure:
The title compound was prepared from (1aR-cis)-1a,7b-dihydro-2,2-dimethyl-2H-oxireno-[c][1]benzopyran-6-carbonitrile (the title A compound of Example 3) and the title A compound by the same procedure as described for the title compound of Example 1. The product was obtained as a colorless solid (0.85 g, 57%), mp 63°-67° C. [α]D =+65.2° (c=0.71 MeOH). Analysis calculated for C23H22N2O3 ·0.25H2O: C, 72.90; H, 5.98; N, 7.39. Found: C, 72.94; H, 5.95; N, 7.35.
Reaction SMILES: Cl[CH2:2][C:3]([NH:5][C:6]1[CH:7]=[N:8][C:9]([O:12][C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[O:19][CH:18]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:17][CH2:16]3)=[CH:10][CH:11]=1)=[O:4].[N-:29]=[N+:30]=[N-:31].[Na+]>C(#N)C>[N:29]([CH2:2][C:3]([NH:5][C:6]1[CH:7]=[N:8][C:9]([O:12][C:13]2[CH:14]=[C:15]3[C:20](=[CH:21][CH:22]=2)[O:19][CH:18]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:17][CH2:16]3)=[CH:10][CH:11]=1)=[O:4])=[N+:30]=[N-:31]
Reactant: [N-]=[N+]=[N-]
Reactant: O=C(CCl)Nc1ccc(Oc2ccc3c(c2)CCC(c2ccccc2)O3)nc1
Agent: [Na+]
Solvent: CC#N
Product: [N-]=[N+]=NCC(=O)Nc1ccc(Oc2ccc3c(c2)CCC(c2ccccc2)O3)nc1
Temperature: 25 °C

Procedure:
2-Chloro-N-[6-(2-phenylchroman-6-yloxy)pyridin-3-yl]acetamide (500 mg), sodium azide (445 mg) and acetonitrile were mixed. Reaction mixture was refluxed for 3 hours. After cooling into room temperature, the reaction mixture was filtered and the filtrate was evaporated to the dryness. 1H-NMR (400 MHz; d6-DMSO) δ: 10.3 (s, 1H), 8.29 (d, 1H, J 2.7 Hz), 8.03 (dd, 1H, J 2.7, 8.8 Hz), 7.47-7.33 (m, 5H), 6.96 (d, 1H, J 8.8 Hz), 6.88-6.85 (m, 3H), 5.12 (dd, 1H, J 2.20, 10.1 Hz), 4.07 (s, 2H), 3.00-2.92 (m, 1H), 2.76-2.70 (m, 1H), 2.19-2.14 (m, 1H), 2.02-1.97 (m, 1H).
Reaction SMILES: O=[C:2]1[C:15]2[CH:14]=[CH:13][C:12]([C:16]([OH:18])=[O:17])=[CH:11][C:10]=2[NH:9][C:8]2[CH2:7][CH2:6][CH2:5][CH2:4][C:3]1=2.P(Cl)(Cl)([Cl:21])=O>>[Cl:21][C:2]1[C:3]2[CH2:4][CH2:5][CH2:6][CH2:7][C:8]=2[N:9]=[C:10]2[C:15]=1[CH:14]=[CH:13][C:12]([C:16]([OH:18])=[O:17])=[CH:11]2
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=C(O)c1ccc2c(=O)c3c([nH]c2c1)CCCC3
Product: O=C(O)c1ccc2c(Cl)c3c(nc2c1)CCCC3
Temperature: 100 °C
Yield: 88 %

Procedure:
A suspension of 9-oxo-5,6,7,8,9,10-hexahydro-acridine-3-carboxylic acid (VIa) (10 g, 4.1 mmols) in phosphorous oxychloride (50 mL) was heated to 100° C. for 1 h. Reaction completion was monitored by TLC. After completion, the reaction mixture was cooled to 25° C. and excess phosphorous oxychloride was removed under vacuum. The residue was mixed with ice (50 g) and the pH was adjusted to 4-5 with solid sodium bicarbonate. The solid obtained was filtered, washed with water (250 mL) and dried under vacuum to get 9.6 g (88%) of compound (Vila) as a white solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([N:18]=O)[CH2:9]2)=[CH:4][CH:3]=1.[Cl-].[NH4+].O.[CH3:23][C:24]([CH3:26])=O>[Zn]>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]([N:18]=[C:24]([CH3:26])[CH3:23])[CH2:9]2)=[CH:4][CH:3]=1
Reactant: CC(C)=O
Reactant: O=NN1CC(c2ccc(F)cc2)Cc2ccccc21
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn]
Solvent: O
Product: CC(C)=NN1CC(c2ccc(F)cc2)Cc2ccccc21
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a solution of 3-(4-fluorophenyl)-1-nitroso-1,2,3,4-tetrahydroquinoline (0.27 g, 0.00105 mol) in acetone (15 mL) was added saturated ammonium chloride solution (1.5 mL) and water (1.5 mL) at RT. The resulting brown colored reaction mixture was cooled to 0° C., and zinc dust (0.411 g, 0.00632 mol) was added portionwise at 0° C. After addition, the reaction mixture was warmed to RT and stirred for 2 h. After completion of reaction (monitored by TLC), the solvent was removed under reduced pressure and the residue extracted with EtOAc (3×100 mL). The organic layer was dried over anhydrous sodium sulfate and solvent was removed under reduced pressure to obtain product as a brown colored oil (0.28 g).
Reaction SMILES: [Cl:1][C:2]1[N:11]=[C:10]([CH3:12])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH2:13]([NH2:16])[CH2:14][CH3:15].C(=O)([O-])[O-].[Na+].[Na+].Cl>C(OCC)C.C(O)C>[ClH:1].[CH3:7][O:6][C:4](=[O:5])[C:3]1[CH:8]=[CH:9][C:10]([CH3:12])=[N:11][C:2]=1[NH:16][CH2:13][CH2:14][CH3:15]
Reactant: COC(=O)c1ccc(C)nc1Cl
Reactant: CCCN
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: CCOCC
Product: CCCNc1nc(C)ccc1C(=O)OC

Procedure:
A stirred mixture of 37.1 g. (0.2 mole) of methyl 2-chloro-6-methyl-nicotinate, 11.8 g. (0.02 mole) of propylamine and 21.2 g. (0.02 mole) of sodium carbonate in 200 ml. of ethanol was heated under reflux for 5 hours. The mixture was filtered and the filtrate was evaporated in a rotary evaporator. The residue was triturated with 200 ml. of water and was extracted with 100 ml. of diethyl ether. The ether layer was dried over magnesium sulfate, filtered and was evaporated to give 31 g. of an oil. A small amount of this oil was dissolved in diethyl ether and was acidified with an etheral hydrochloric acid solution. On cooling, the oil which separated crystallized to yield 6-methyl-2-propylaminonicotinic acid methyl ester, hydrochloride. The solid was collected and was recrystallized from ethyl acetate to give the analytical sample, m.p. 113°-15° C.
Reaction SMILES: [C:1]([O:6][CH2:7][CH2:8][N:9]=[C:10]=[O:11])(=[O:5])[C:2]([CH3:4])=[CH2:3].[C:12]([O:16][CH2:17][CH2:18][OH:19])(=[O:15])[CH:13]=[CH2:14]>C([O-])(=O)CCCCCCCCCCC.C([O-])(=O)CCCCCCCCCCC.C([Sn+2]CCCC)CCC>[CH3:3][C:2](=[CH2:4])[C:1]([O:6][CH2:7][CH2:8][NH:9][C:10]([O:19][CH2:18][CH2:17][O:16][C:12](=[O:15])[CH:13]=[CH2:14])=[O:11])=[O:5]
Reactant: C=CC(=O)OCCO
Reactant: C=C(C)C(=O)OCCN=C=O
Agent: CCCCCCCCCCCC(=O)[O-]
Agent: CCCC[Sn+2]CCCC
Product: C=CC(=O)OCCOC(=O)NCCOC(=O)C(=C)C
Reaction time: 8 h

Procedure:
In a 4 ounce glass jar were mixed 2-isocyanatoethyl methacrylate (15.5 g, 0.10 mol, available from Aldrich), 2-hydroxyethyl acrylate (11.6 g, 0.10 mol, available from Aldrich), and one drop of di-n-butyltin dilaurate (available from Alfa Aesar) to cause a slight exotherm. The jar was cooled briefly in an ice bath, and then left at room temperature overnight. NMR and IR spectral analyses confirmed the structure of the product.
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1B(O)O.C[O:16][C:17](=[O:46])[CH2:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([O:33][C:34]3[CH:39]=[CH:38][C:37]([C:40]([F:43])([F:42])[F:41])=[CH:36][C:35]=3Br)[CH:28]=2)=[CH:22][C:21]=1[CH3:45]>>[CH3:45][C:21]1[CH:22]=[C:23]([O:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([O:33][C:34]3[CH:39]=[CH:38][C:37]([C:40]([F:42])([F:43])[F:41])=[CH:36][C:35]=3[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[O:3][C:2]([F:14])([F:13])[F:1])[CH:28]=2)[CH:24]=[CH:25][C:20]=1[CH2:19][CH2:18][C:17]([OH:46])=[O:16]
Reactant: OB(O)c1ccccc1OC(F)(F)F
Reactant: COC(=O)CCc1ccc(Oc2cccc(Oc3ccc(C(F)(F)F)cc3Br)c2)cc1C
Product: Cc1cc(Oc2cccc(Oc3ccc(C(F)(F)F)cc3-c3ccccc3OC(F)(F)F)c2)ccc1CCC(=O)O

Procedure:
The title compound is prepared according to Example 89 by using 2-trifluoromethoxyphenyl boronic acid and 3-{4-[3-(2-bromo-4-trifluoromethyl-phenoxy)-phenoxy]-2-methyl-phenyl}-propionic acid methyl ester to afford about 94 mg (58%). 1H NMR (400 MHz, CDCl3); MS (ES+) m/z mass calcd for C30H22O5F6 576, found 577 (M+1, 100%).
Reaction SMILES: P(Br)(Br)Br.[CH3:5][S:6][C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[CH2:9]O.[C-:15]#[N:16].[Na+]>C1(C)C=CC=CC=1.O.C(O)C>[CH3:5][S:6][C:7]1[CH:14]=[CH:13][CH:12]=[CH:11][C:8]=1[CH2:9][C:15]#[N:16]
Reactant: CSc1ccccc1CO
Reactant: [C-]#N
Agent: BrP(Br)Br
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Solvent: CCO
Product: CSc1ccccc1CC#N
Temperature: 40 °C
Reaction time: 1 h

Procedure:
Phosphorus tribromide (75 g) in toluene (50 ml) was added to a stirred mixture of 2-methylthiobenzyl alcohol (42.5 g) in toluene (25 ml) over 10 minutes at 5° C. The mixture was then stirred at 40° C. for 1 hour, water (100 ml) was added and stirring continued at ambient temperature for 1 hour. The organic layer was separated and the aqueous layer extracted with ethyl acetate. The combined organic layers yielded an oil. The oil (58.6 g) was dissolved in a 1:2 mixture of water and ethanol and sodium cyanide (26.5 g) was added over 15 minutes. The mixture was stirred at 50° C. for 1.5 hours then poured onto water (500 ml) and extracted with ethyl acetate. The extract yielded 2-methylthiophenylacetonitrile.
Reaction SMILES: [SH:1][C:2]1[N:3]([NH2:20])[C:4]([C@H:7]([NH:9][C:10](=[O:19])[O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH3:8])=[N:5][N:6]=1.[Cl:21][C:22]1[CH:23]=[C:24]([N:28]=[C:29]=S)[CH:25]=[CH:26][CH:27]=1.C1(N=C=NC2CCCCC2)CCCCC1>C(O)C.CCOCC>[Cl:21][C:22]1[CH:23]=[C:24]([NH:28][C:29]2[S:1][C:2]3=[N:6][N:5]=[C:4]([C@H:7]([NH:9][C:10](=[O:19])[O:11][CH2:12][C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[CH3:8])[N:3]3[N:20]=2)[CH:25]=[CH:26][CH:27]=1
Reactant: S=C=Nc1cccc(Cl)c1
Reactant: C[C@@H](NC(=O)OCc1ccccc1)c1nnc(S)n1N
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CCOCC
Solvent: CCO
Product: C[C@@H](NC(=O)OCc1ccccc1)c1nnc2sc(Nc3cccc(Cl)c3)nn12
Temperature: 80 °C
Reaction time: 4 h
Yield: 48.7 %

Procedure:
(Step 8-ii) A mixture of (R)-benzyl 1-(5-mercapto-4-amino-4H-1,2,4-triazol-3-yl)ethylcarbamate (1.32 g, 4.5 mmol) in ethanol (15 mL) was heated to 80° C. and 3-chlorophenylisothiocyanate (1.3 g, 7.65 mmol) and dicyclohexylcarbodiimide (1.11 g, 5.4 mmol) were added. After 4 hours, the reaction was cooled, diluted with an equal volume of ether, and filtered. The filter cake was washed with additional ether and the collected solids dried in vacuo to provide 0.94 g of (R)-benzyl 1-(6-(3-chlorophenylamino)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl)ethylcarbamate: ESMS MH+=429.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][C:6]([NH2:12])=[C:5]2[NH:13][C:14]1[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=1[O:22][CH3:23].C[S-](C)[C:26]([S-])=[N:27][C:28]#[N:29].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[Br:1][C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[NH:12][C:26](=[N:27][C:28]#[N:29])[N:13]([C:14]4[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][C:15]=4[O:22][CH3:23])[C:5]=3[C:4]=2[CH:3]=1
Reactant: C[S-](C)C([S-])=NC#N
Reactant: COc1ccc(Nc2c(N)cnc3ccc(Br)cc23)c(OC)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: COc1ccc(-n2c(=NC#N)[nH]c3cnc4ccc(Br)cc4c32)c(OC)c1
Temperature: 80 °C

Procedure:
To the stirred solution of 6-bromo-N4-(2,4-dimethoxyphenyl)quinoline-3,4-diamine (10.69 mmol) in DMF (10 mL) was added dimethylcyanocarbonimidodithioate (16.03 mmol) followed by cesium carbonate (32.1 mmol) and the resulting reaction mixture was heated at 80° C. for 18 h. Completion of reaction was monitored by TLC, solvent evaporated under reduced pressure. Residue was diluted with water & extracted with ethyl acetate (250 mlx 5), organic layer were dried over anhydrous Na2SO4 and evaporated under vacuum. Crude product was further purified on silica gel column using MeOH/CHCl3 (8%) as elute to afford desired product as off-white solid. 1H NMR (300 MHz, DMSO-d6): δ 13.72 (s, 1H), 8.93 (s, 1H), 8.03 (d, J=9 Hz, 1H), 7.77 (dd, J=3.9 Hz, 1H), 7.58 (d, J=9 Hz, 1H), 7.16 (d, J=3 Hz, 1H), 6.93 (d, J=3 Hz, 1H), 6.84 (dd, J=3, 9 Hz, 1H), 3.92 (s, 3H), 3.69 (s, 3H); MS (m/z): 424 (M+1)+.
Reaction SMILES: S1[CH:5]=[CH:4][C:3]([C:6]2[CH:7]=[C:8]3[C:14]([C:15]4[CH:16]=[C:17]([CH:38]=[CH:39][CH:40]=4)[CH2:18][NH:19][C:20]([C:22]4[C:23](=[O:37])[N:24]([CH2:28][C:29]5[CH:34]=[CH:33][C:32]([F:35])=[C:31]([F:36])[CH:30]=5)[CH:25]=[CH:26][CH:27]=4)=[O:21])=[CH:13][NH:12][C:9]3=[N:10][CH:11]=2)=[CH:2]1.[N:41]1C=CC(B(O)O)=C[CH:42]=1.B(O)O>>[N:41]1[CH:5]=[CH:4][C:3]([C:6]2[CH:7]=[C:8]3[C:14]([C:15]4[CH:16]=[C:17]([CH:38]=[CH:39][CH:40]=4)[CH2:18][NH:19][C:20]([C:22]4[C:23](=[O:37])[N:24]([CH2:28][C:29]5[CH:34]=[CH:33][C:32]([F:35])=[C:31]([F:36])[CH:30]=5)[CH:25]=[CH:26][CH:27]=4)=[O:21])=[CH:13][NH:12][C:9]3=[N:10][CH:11]=2)=[CH:2][CH:42]=1
Reactant: O=C(NCc1cccc(-c2c[nH]c3ncc(-c4ccsc4)cc23)c1)c1cccn(Cc2ccc(F)c(F)c2)c1=O
Reactant: OB(O)c1ccncc1
Agent: OBO
Product: O=C(NCc1cccc(-c2c[nH]c3ncc(-c4ccncc4)cc23)c1)c1cccn(Cc2ccc(F)c(F)c2)c1=O

Procedure:
Except where indicated, 1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid 3-(5-pyridin-4-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-benzylamide was synthesized as per Example 91, 1-(3,4-Difluoro-benzyl)-2-oxo-1,2-dihydro-pyridine-3-carboxylic acid 3-(5-thiophen-3-yl-1H-pyrrolo[2,3-b]pyridin-3-yl)-benzylamide using 4-Pyridylboronic acid as boronic acid to yield the product. 1H NMR (400 MHz, DMSO-d6) d ppm 12.280 (s, 1H) 10.090 (t, J=6.0 Hz, 1H) 8.864-8.712 (m, 4H) 8.384 (d, J=7.4 Hz, 1H) 8.302-8.233 (m, 2H) 8.201 (d, J=6.5 Hz, 1H) 7.983 (s, 1H) 7.797 (s, 1H) 7.694 (d, J=7.4 Hz, 1H) 7.458-7.302 (m, 3H) 7.239 (d, J=7.0 Hz, 1H) 7.134-7.079 (m, 1H) 6.567 (t, J=7.0 Hz, 1H) 5.146 (s, 2H) 4.605 (d, J=5.6 Hz, 2H); MS m/z/z=548.29 M+H.