Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([N:14]1[C:22]2[C:17](=[C:18]([OH:23])[CH:19]=[CH:20][CH:21]=2)[CH:16]=[C:15]1[C:24]([O:26][CH3:27])=[O:25])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.Br[CH2:29][CH2:30][OH:31]>CN(C=O)C>[CH2:7]([N:14]1[C:22]2[C:17](=[C:18]([O:23][CH2:29][CH2:30][OH:31])[CH:19]=[CH:20][CH:21]=2)[CH:16]=[C:15]1[C:24]([O:26][CH3:27])=[O:25])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: OCCBr
Reactant: COC(=O)c1cc2c(O)cccc2n1Cc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1cc2c(OCCO)cccc2n1Cc1ccccc1
Temperature: 80 °C
Reaction time: 16 h

Procedure:
Potassium carbonate (0.2 g) was added to a stirred solution of methyl N-benzyl-4-hydroxyindole-2-carboxylate (0.2 g) and 2-Bromoethanol (98 mg) in DMF (15 ml). The reaction was then stirred for 16 hours at 80° C. under an atmosphere of argon. The reaction mixture was concentrated in vacuo and the residue partitioned between ethyl acetate and water. Combined organic extracts were washed with water, dried (MgSO4), concentrated in vacuo and the residue purified by column chromatography using 70% ethyl acetate: isohexane as eluent to give the product as a colourless crystalline solid. (64 mg, 27%); NMR d (CD3SOCD3) 3.74-3.82 (m, 5H), 4.10 (m, 2H), 4.88 (m, 1H), 5.80 (s, 2H), 6.58 (m, 1H), 6.98 (d, 2H), 7.09 (m, 1H), 7.14-7.27 (m, 4H), 7.38 (m, 1H); M/z (+) 326 (MH+).
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([CH2:7][C:8]([OH:10])=O)=[CH:3][CH:2]=1.[NH2:12][C:13]1[S:14][C:15]([CH3:18])=[CH:16][N:17]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>ClCCl>[CH3:18][C:15]1[S:14][C:13]([NH:12][C:8](=[O:10])[CH2:7][C:4]2[CH:3]=[CH:2][C:1]([CH3:11])=[CH:6][CH:5]=2)=[N:17][CH:16]=1
Reactant: Cc1ccc(CC(=O)O)cc1
Reactant: Cc1cnc(N)s1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1ccc(CC(=O)Nc2ncc(C)s2)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 90.2 %

Procedure:
To a suspension of p-tolylacetic acid (1.00 g, 6.66 mmol) and 2-amino-5-methylthiazole (0.760 g, 6.66 mmol) in dichloromethane (10 mL) was added at 0° C. under a nitrogen atmosphere 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.40 g, 7.32 mmol), 1-hydroxybenzotriazole (90 mg, 0.67 mmol) and N,N-diisopropyl ethyl amine (1.8 mL, 10 mmol). The ice bath was removed and the resulting solution was stirred for 3 h at ambient temperature. The reaction mixture was diluted with dichloromethane (20 mL) and washed with aqueous sodium carbonate (half-concentrated, 20 mL) and water (20 mL). The aqueous layers were extracted with dichloromethane (20 mL) and the combined organic layers were dried over sodium sulfate. The filtrate was concentrated and the residue was suspended in TBME (20 mL) and filtered. Washing with TBME (10 mL) afforded the title compound (1.48 g, 90%) as a white solid. MS m/e: 247.2 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5](I)=[CH:4][N:3]=1.CC1(C)C(C)(C)OB([C:41]2[CH:45]=[CH:44][S:43][C:42]=2[CH:46]=[O:47])O1>>[NH2:1][C:2]1[C:7]2[C:8]([C:11]3[CH:16]=[CH:15][C:14]([NH:17][C:18]([C:20]4[N:21]([CH3:29])[C:22]5[C:27]([CH:28]=4)=[CH:26][CH:25]=[CH:24][CH:23]=5)=[O:19])=[C:13]([O:30][CH3:31])[CH:12]=3)=[CH:9][S:10][C:6]=2[C:5]([C:41]2[CH:45]=[CH:44][S:43][C:42]=2[CH:46]=[O:47])=[CH:4][N:3]=1
Reactant: CC1(C)OB(c2ccsc2C=O)OC1(C)C
Reactant: COc1cc(-c2csc3c(I)cnc(N)c23)ccc1NC(=O)c1cc2ccccc2n1C
Product: COc1cc(-c2csc3c(-c4ccsc4C=O)cnc(N)c23)ccc1NC(=O)c1cc2ccccc2n1C

Procedure:
N-[4-(4-amino-7-iodothieno[3,2-c]pyridin-3-yl)-2-methoxyphenyl]-1-methyl-1H-indole-2-carboxamide and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carbaldehyde were reacted together according to general procedure A to furnish the title compound. LCMS (Conditions a): MH+=539.0, RT=4.10 minutes; 1H NMR (DMSO-d6, 400 MHz) δ 9.77 (s, 1H), 9.53 (s, 1H), 8.29 (d, J=5.3 Hz, 1H), 7.98 (m, 2H), 7.63 (m, 6H), 7.36 (m, 1H), 7.24 (s, 1H), 7.15 (m, 1H), 5.85 (br, 2H), 4.04 (s, 3H), 3.92 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:16](=[O:21])C(F)(F)F)=[CH:7][N:8]2[CH2:11][C:12]([NH:14][CH3:15])=[O:13])=[CH:4][CH:3]=1.C[Si](C)(C)[O-:24].[Na+]>ClCCCl>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:16]([OH:21])=[O:24])=[CH:7][N:8]2[CH2:11][C:12](=[O:13])[NH:14][CH3:15])=[CH:4][CH:3]=1
Reactant: CNC(=O)Cn1cc(C(=O)C(F)(F)F)c2ccc(Cl)cc21
Reactant: C[Si](C)(C)[O-]
Agent: [Na+]
Solvent: ClCCCl
Product: CNC(=O)Cn1cc(C(=O)O)c2ccc(Cl)cc21
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 27 %

Procedure:
2-[6-Chloro-3-(2,2,2-trifluoro-acetyl)-indol-1-yl]-N-methyl-acetamide was suspensed in DCE and treated with (2.2 eq.) of sodium trimethylsilanolate. After shaking at room temperature for 20 min, the mixture was concentrated in vacuo and purified by prep. HPLC to give the title compound in 27% yield.
Reaction SMILES: [CH2:1]([C:3]1([O:35][C:36](=[O:45])[O:37][CH2:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[C:8]2[CH:9]=[C:10]3[N:18]([C:19](=[O:20])[C:7]=2[CH2:6][O:5][C:4]1=[O:34])[CH2:17][C:16]1[C:15]([CH2:21][CH2:22][Si:23]([CH2:26][CH2:27][CH2:28][OH:29])([CH3:25])[CH3:24])=[C:14]2[CH:30]=[CH:31][CH:32]=[CH:33][C:13]2=[N:12][C:11]3=1)[CH3:2].[CH:46]1([C:50](Cl)=[O:51])[CH2:49][CH2:48][CH2:47]1>CN(C)C1C=CN=CC=1.ClCCl>[CH2:38]([O:37][C:36]([O:35][C:3]1([CH2:1][CH3:2])[C:8]2[CH:9]=[C:10]3[N:18]([C:19](=[O:20])[C:7]=2[CH2:6][O:5][C:4]1=[O:34])[CH2:17][C:16]1[C:15]([CH2:21][CH2:22][Si:23]([CH3:25])([CH3:24])[CH2:26][CH2:27][CH2:28][O:29][C:50]([CH:46]2[CH2:49][CH2:48][CH2:47]2)=[O:51])=[C:14]2[CH:30]=[CH:31][CH:32]=[CH:33][C:13]2=[N:12][C:11]3=1)=[O:45])[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1
Reactant: CCC1(OC(=O)OCc2ccccc2)C(=O)OCc2c1cc1n(c2=O)Cc2c-1nc1ccccc1c2CC[Si](C)(C)CCCO
Reactant: O=C(Cl)C1CCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CCC1(OC(=O)OCc2ccccc2)C(=O)OCc2c1cc1n(c2=O)Cc2c-1nc1ccccc1c2CC[Si](C)(C)CCCOC(=O)C1CCC1
Temperature: 21 °C
Reaction time: 5 h

Procedure:
A mixture of Compound 53 (70 mg, 0.11 mmol), 4-dimethylaminopyridine (27 mg, 0.22 mmol), and cyclobutanecarbonyl chloride (26 mg, 0.22 mmol) in 2.0 mL of dichloromethane was stirred at 21° C. for 5 hours. The reaction was quenched with saturated sodium bicarbonate solution, and aqueous layer was extracted with dichloromethane. The combined organic layers were dried over sodium sulfate and concentrated to afford a crude product, which was chromatographed to give the desired product.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[C:6]([Cl:11])[C:5]=1[OH:12].S1(=O)(=O)[N:17]2[CH2:18][CH2:19][CH2:20][C@H:16]2[CH2:15]O1.Cl>CN(C)C=O>[Cl:3][C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[C:6]([Cl:11])[C:5]=1[O:12][CH2:15][C@@H:16]1[CH2:20][CH2:19][CH2:18][NH:17]1
Reactant: Oc1c(Cl)cc(Cl)cc1Cl
Reactant: O=S1(=O)OC[C@@H]2CCCN21
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Clc1cc(Cl)c(OC[C@@H]2CCCN2)c(Cl)c1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 42.2 %

Procedure:
Sodium hydride 55% in oil (1.4 g; 29.8 mmol) was added portionwise over 10 minutes to a stirred solution of 2,4,6-trichlorophenol (5.89 g; 29.8 mmol) in dry dimethylformamide (90 ml) at a temperature of 10° C. under nitrogen. The reaction mixture was stirred for 20 minutes at ambient temperature followed by the addition of (S)-tetrahydro-pyrrolo[1,2-c][1,2,3]oxathiazole 1,1-dioxide (5.0 g; 30.6 mmol), which was prepared as described in example P14, in dimethylformamide (25 ml). The reaction mixture was stirred for 4 hours at ambient temperature then poured onto 1M HCl (400 ml) and extracted with ethyl acetate (2×200 ml). The combined ethyl acetate layers are washed with water (2×100 ml), saturated NaCl (100 ml) and then dried over Na2SO4. After removal of the solvent the residue (11.1 g oil) was dissolved in dioxane (150 ml) and treated with sulphuric acid (2.9 ml) and water (2.9 ml). The reaction mixture was stirred at ambient temperature for 15 hours. The reaction mixture was poured on sat. NaHCO3 (300 ml) and extracted with dichloromethane (3×200 ml). The organic layers are washed with saturated NaCl (100 ml) and then dried over Na2SO4. After evaporation of the solvent, the crude product (7.16 g in the form of a orange oil) was purified by flash chromatography over silica gel (eluent:dichloromethane/methanol 9:1) to afford 3.53 g (42.0% of theory) of (S)-2-(2,4,6-trichloro-phenoxymethyl)-pyrrolidine as a oil.
Reaction SMILES: [C:1]1([SH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[O:8]1[CH2:12][CH2:11]OC1=O>>[C:1]1([S:7][CH2:11][CH2:12][OH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C1OCCO1
Reactant: Sc1ccccc1
Product: OCCSc1ccccc1

Procedure:
Benzenethiol is reacted with 1,3-dioxolan-2-one to form 2-(phenylthio)ethanol. The 2-(phenylthio)ethanol is isolated and then converted to 2-(phenylthio)ethanethiol using triphenylphosphine, diisopropyl azodicarboxylate (DIAD), and thiolacetic acid followed by hydrolysis of the resulting acetate with potassium hydoxide in methanol.
Reaction SMILES: Br[CH2:2][C:3]([CH2:5]Br)=[O:4].[Cl:7][C:8]1[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:9]=1[C:10](O)=[O:11].[F-].[K+]>CN(C)C=O>[Cl:7][C:8]1[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:9]=1[CH2:10][O:11][CH2:2][C:3]([CH2:5][O:11][CH2:10][C:9]1[C:8]([Cl:7])=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:17])=[O:4]
Reactant: O=C(O)c1c(Cl)cccc1Cl
Reactant: O=C(CBr)CBr
Agent: [F-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C(COCc1c(Cl)cccc1Cl)COCc1c(Cl)cccc1Cl
Temperature: 25 °C
Reaction time: 2 h

Procedure:
The bromomethylketone derivative (4.36 g) and 2,6-dichlorobenzoic acid (2.28 g, 1.1 eq) were dissolved in dimethylformamide (18 mL), KF (1.58 g, 2.5 eq) was added thereto, and the mixture was stirred for 2 h at room temperature. The residue obtained by concentration under reduced pressure was extracted with ethyl acetate, washed with water, twice with saturated aqueous sodium hydrogen carbonate solution, and aqueous sodium chloride solution, dried (anhydrous Na2SO4), and concentrated under reduced pressure to give the 2,6-dichlorobenzoxymethylketone derivative. This compound was dissolved in methanol (20 mL), and reacted by adding NaBH4 (412 mg)-methanol solution (40 mL). The reaction mixture was slowly warmed to room temperature for 2 h. The reaction was stopped by acetic acid. The reaction mixture was distilled under reduced pressure to remove methanol, extracted with ethyl acetate (50 mL×2), washed with water and aqueous sodium chloride solution, dried (anhydrous Na2SO4), concentrated under reduced pressure, and separated by column chromatography (ethyl acetate-hexane, 1:5) to give 4.80 g (86%) of the title compound.
Reaction SMILES: [CH2:1]([N:8]1[CH2:12][CH2:11][CH:10]([N:13]=[N+:14]=[N-:15])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:16]1([C:22]#[CH:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(Cl)(Cl)Cl.CCCCCC>C1C=CC=CC=1.CO>[CH2:1]([N:8]1[CH2:12][CH2:11][CH:10]([N:13]2[C:22]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:23][N:15]=[N:14]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [N-]=[N+]=NC1CCN(Cc2ccccc2)C1
Reactant: C#Cc1ccccc1
Solvent: CCCCCC
Solvent: CO
Solvent: c1ccccc1
Product: c1ccc(CN2CCC(n3nncc3-c3ccccc3)C2)cc1

Procedure:
A solution of N-benzyl-3-azido pyrrolidine (3 g, 0.0148 mol) and phenyl-acetylene (3 g, 0.0292 mol) in benzene (30 ml) was heated under reflux for 48 hrs. The reaction mixture was concentrated to oil from which the title compounds were isolated by column chromatography using silica gel and a mixture of CHCl3, hexane, MeOH (4:4:1) as eluant. N-benzyl-3-(5-phenyl-1,2,3-triazol-1-yl)pyrrolidine was obtained as oil. Yield: 1 g (22.17%). 1H NMR (CDCl3) δ: 2.32-2.51 (m, 2H), 2.88-3.13 (m, 2H), 3.80 (s, 2H), 5.00 (p, 1H), 7.20-7.53 (m, 10H), 7.67 (s, 1H). N-benzyl-3-(4-phenyl-1,2,3-triazol-1-yl)pyrrolidine, oil, yield 3.0 g. 1H NMR (CDCl3) δ: 2.05-2.22 (m, 1H), 2.30-2.69 (m, 2H), 2.75-3.25 (m, 3H), 5.20- 5.33 (m, 1H), 7.23-7.51 (m, 8H), 7.81-7.92 (m, 2H), 8.06 (s, 1H).
Reaction SMILES: [C:1]([NH:4][C@H:5]([CH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:19][CH:18]=1)[C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]([OH:15])=O)=[O:7])(=[O:3])[CH3:2].[NH2:29][CH2:30][C:31]1[CH:32]=[C:33]2[C:38](=[CH:39][CH:40]=1)[C:37]([NH2:41])=[N:36][CH:35]=[CH:34]2.CN1CCOCC1.F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1>CN(C)C=O>[NH2:41][C:37]1[C:38]2[C:33](=[CH:32][C:31]([CH2:30][NH:29][C:13]([C@@H:9]3[CH2:10][CH2:11][CH2:12][N:8]3[C:6](=[O:7])[C@H:5]([NH:4][C:1](=[O:3])[CH3:2])[CH2:16][C:17]3[CH:18]=[CH:19][C:20]([C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=4)=[CH:21][CH:22]=3)=[O:15])=[CH:40][CH:39]=2)[CH:34]=[CH:35][N:36]=1
Reactant: CC(=O)N[C@H](Cc1ccc(-c2ccccc2)cc1)C(=O)N1CCC[C@H]1C(=O)O
Reactant: NCc1ccc2c(N)nccc2c1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: CC(=O)N[C@H](Cc1ccc(-c2ccccc2)cc1)C(=O)N1CCC[C@H]1C(=O)NCc1ccc2c(N)nccc2c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 71 %

Procedure:
A mixture of 1-(2-(R)-acetylamino-3-biphenyl-4yl-propionyl)-pyrrolidine-2-(S)-carboxylic acid (0.120 g), 6-aminomethyl-isoquinolin-1-ylamine (0.058 g), N-methyl morpholine (0.11 mL) and 0.100 g of 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) in 4.5 mL of dry N,N-dimethyl formamide was stirred for 3 h at ambient temperature. The mixture was concentrated and the remaining residue was purified by silica chromatography (dichloro-methane/methanol 8/2) to give 0.120 g (70%) of the title compound as a light yellow solid. (+)-APCI-MS: 536 (MH+).
Reaction SMILES: [C:1]1([SH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH2:10]([O:12][C:13]([C@@H:15]1[CH2:19][C@H:18](OS(C)(=O)=O)[CH2:17][C@H:16]1[C:25]([N:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1)=[O:26])=[O:14])[CH3:11]>C1COCC1>[CH2:10]([O:12][C:13]([C@@H:15]1[CH2:19][C@@H:18]([S:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:17][C@H:16]1[C:25]([N:27]1[CH2:28][CH2:29][O:30][CH2:31][CH2:32]1)=[O:26])=[O:14])[CH3:11]
Reactant: CCOC(=O)[C@@H]1C[C@H](OS(C)(=O)=O)C[C@H]1C(=O)N1CCOCC1
Reactant: Sc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOC(=O)[C@@H]1C[C@@H](Sc2ccccc2)C[C@H]1C(=O)N1CCOCC1

Procedure:
To a solution of the thiophenol (0.41 mmol) in THF (4 ml) was added NaH (55% in oil, 0.41 mmol) at 22° C. and stirring was continued until gas evolution ceased. To the mixture was added a solution of (1R,2R,4R)-4-methanesulfonyloxy-2-(morpholine-4-carbonyl)-cyclopentanecarboxylic acid ethyl ester (0.28 mmol) in THF (4 ml) and stirring was continued at 50° C. until completion of the reaction. The mixture was partitioned between ethyl acetate and water, the organic layer was dried, evaporated and the residue chromatographed on silica using mixtures of cyclohexane and ethyl acetate to give the title compound as pale yellow oil. MS: 364.5 (M+H)+.
Reaction SMILES: Cl[C:2]1[N:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].C(=O)([O-])[O-].[K+].[K+].Cl.Cl.[N:20]1[CH:25]=[CH:24][CH:23]=[N:22][C:21]=1[N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1>CN(C=O)C>[N:20]1[CH:25]=[CH:24][CH:23]=[N:22][C:21]=1[N:26]1[CH2:31][CH2:30][N:29]([C:2]2[N:11]=[CH:10][CH:9]=[CH:8][C:3]=2[C:4]([O:6][CH3:7])=[O:5])[CH2:28][CH2:27]1
Reactant: COC(=O)c1cccnc1Cl
Reactant: c1cnc(N2CCNCC2)nc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1cccnc1N1CCN(c2ncccn2)CC1

Procedure:
3.4 g of methyl chloronicotinate, 11.1 g of potassium carbonate and 4.7 g of N-(2-pyrimidyl)piperazine dihydrochloride were reacted in 75 ml of DMF analogously to Example 1a, 4.6 g (78%) of the product being obtained.
Reaction SMILES: [NH:1]1[C:9]2[CH:8]=[CH:7][CH:6]=[C:5]([C:10]([O:12][CH3:13])=[O:11])[C:4]=2[CH:3]=[CH:2]1.CO[CH:16]1[CH2:20][CH2:19][CH:18](OC)O1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH:8]1[C:9]2[NH:1][C:2]3[C:3](=[CH:18][CH:19]=[CH:20][CH:16]=3)[C:4]=2[C:5]([C:10]([O:12][CH3:13])=[O:11])=[CH:6][CH:7]=1
Reactant: COC(=O)c1cccc2[nH]ccc12
Reactant: COC1CCC(OC)O1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Product: COC(=O)c1cccc2[nH]c3ccccc3c12
Yield: 13.5 %

Procedure:
A mixture of 52.56 g of methyl indole-4-carboxylate, 51.55 g of 2,5-dimethoxytetrahydrofuran and 28.53 g of p-toluenesulfonic acid monohydrate in 300 ml of methanol was refluxed for 10 hours. Then, following a treatment similar to that of Example 1(1), there was obtained 9.14 g of methyl carbazole-4-carboxylate.
Reaction SMILES: C([O:8][C:9]1[CH:10]=[C:11]([N:15]2[C:19]3[C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][C:25]=4[S:26](=[O:29])(=[O:28])[CH2:27][C:18]=3[C:17]([C:30]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[O:31])=[N:16]2)[CH:12]=[CH:13][CH:14]=1)C1C=CC=CC=1.[H][H]>CO.[Pd]>[N:32]1([C:30]([C:17]2[C:18]3[CH2:27][S:26](=[O:28])(=[O:29])[C:25]4[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=4[C:19]=3[N:15]([C:11]3[CH:10]=[C:9]([OH:8])[CH:14]=[CH:13][CH:12]=3)[N:16]=2)=[O:31])[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1
Reactant: O=C(c1nn(-c2cccc(OCc3ccccc3)c2)c2c1CS(=O)(=O)c1ccccc1-2)N1CCOCC1
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: O=C(c1nn(-c2cccc(O)c2)c2c1CS(=O)(=O)c1ccccc1-2)N1CCOCC1
Yield: 7.4 %

Procedure:
To a solution 1-[3-(benzyloxy)phenyl]-3-(morpholin-4-ylcarbonyl)-1,4-dihydrothiochromeno[4,3-c]pyrazole 5,5-dioxide (8 g, 155 mmol) in MeOH (500 mL) is added 10% Pd/C (0.5 g) and the reaction mixture is hydrogenated at 12 Kg/cm2 pressure of hydrogen at RT for 20 h in Autoclave. The catalyst is filtered through celite and filtrate is concentrated to afford 4.9 g (89%) of the title compound as a brown solid. 1H NMR (DMSO-d6, 400 MHz): δ 10.08 (s, 1H), 8.02-8.00 (dd, J=2.4, 3.2 Hz, 1H), 7.65-7.59 (m, 2H), 7.42-7.38 (t, J=8.0 Hz, 1H), 7.01-6.99 (t, J=8.4 Hz, 1H), 6.93-6.88 (m, 3H), 4.88 (s, 2H), 3.95 (m, 2H), 3.66-3.61 (m, 4H), 3.56 (s, 2H). MS (ESI+): 426.0. HPLC (max plot): 96%; Rt 3.25 min.
Reaction SMILES: O[CH2:2][CH2:3][C:4]([NH2:6])=[O:5].[CH2:7](N)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.N>C(C1C(O)=C(C(C)(C)C)C=C(C)C=1)(C)(C)C>[CH2:7]([NH:6][C:4](=[O:5])[CH:3]=[CH2:2])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: NC(=O)CCO
Reactant: NCc1ccccc1
Agent: Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Agent: N
Product: C=CC(=O)NCc1ccccc1
Yield: 86.2 %

Procedure:
59 g of β-hydroxypropionamide and 75 g of benzylamine were heated with 50 mg of 2,6-di-t-butyl-p-cresol for 7 hours in a temperature range of 120°-170° C. until the evolution of ammonia was complete. After adding 2.2 g of polyphosphoric acid distillation was carried out in an oil pump vacuum; the subsequent redistillation with the addition of 1 ml of sulphuric acid yielded 92 g of N-benzylacrylamide, Bp0.1 113° C., which crystallized in the receiver. Mp (crude product): 53° C.
Reaction SMILES: [O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8].[CH2:14]([Mg]Br)[CH:15]([CH3:17])[CH3:16].C(OCC)C>O1CCCC1>[CH3:11][C:10]([O:9][C:7](=[O:8])[NH:3][CH2:4][CH2:5][CH2:6][C:2](=[O:1])[CH2:14][CH:15]([CH3:17])[CH3:16])([CH3:13])[CH3:12]
Reactant: CC(C)C[Mg]Br
Reactant: CC(C)(C)OC(=O)N1CCCC1=O
Solvent: C1CCOC1
Solvent: CCOCC
Product: CC(C)CC(=O)CCCNC(=O)OC(C)(C)C

Procedure:
A solution of 1,1-dimethylethyl 2-oxo-1-pyrrolidinecarboxylate (7.5 g, 40.5 mmol) in dry tetrahydrofuran (150 ml) under a nitrogen atmosphere and at −78° C., was treated dropwise with a solution of isobutyl magnesium bromide in diethyl ether (2 molar, 22.5 ml, 45 mmol). The mixture was stirred at −78° C. for 2h then quenched into a saturated aqueous solution of ammonium chloride (100 ml). The products were extracted into ethyl acetate (2×250 ml) and the combined extracts dried over magnesium sulphate. Concentration of the extracts gave an oil which was purified on silica gel using isohexane/diethylether (1:1). The title compound was isolated as a colourless oil (2.3 g, 25%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]([OH:9])[C:4](C2C=CC=CC=2)([N:10]=NC2C=CC=CC=2O)[CH:3]=1>C(OCC)(=O)C.[Pd]>[NH2:10][C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([CH3:8])[C:5]=1[OH:9]
Reactant: CC1=CC(F)=CC(N=Nc2ccccc2O)(c2ccccc2)C1O
Agent: [Pd]
Solvent: CCOC(C)=O
Product: Cc1cc(F)cc(N)c1O
Temperature: 25 °C
Reaction time: 17.5 h
Yield: 90.7 %

Procedure:
A mixture of 5.75 g (25 mmoles) of 4-fluoro-6-methyl-2-phenylazophenol (B1) and 1.1 g of 5% Pd/c in ethyl acetate was shaken in a Parr shaker under hydrogen at room temperature for 17.5 hours. The reaction mixture was filtered through celite and the filtrate concentrated to an oil which was purified on silica gel eluting with hexane-ethyl acetate, giving 3.2 g of a white solid: m.p. 97° C. (dec).
Reaction SMILES: [CH3:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9](=[O:27])[CH:10]=[CH:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[C:14]([O:25][CH3:26])[CH:13]=2)[CH2:4][CH2:3]1>[C].[Pd].CO>[CH3:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9](=[O:27])[CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[C:14]([O:25][CH3:26])[CH:13]=2)[CH2:4][CH2:3]1
Reactant: COc1cc(C=CC(=O)N[C@H]2CC[C@H](C)CC2)ccc1OCCCC(=O)O
Agent: [Pd]
Solvent: CO
Product: COc1cc(CCC(=O)N[C@H]2CC[C@H](C)CC2)ccc1OCCCC(=O)O

Procedure:
Using 0.2 g of N-(trans-4-methylcyclohexyl)-4-(3-carboxypropoxy) -3-methoxycinnamamide (Example 175), 0.01 g of 10% palladium-carbon, and 35 ml of methanol, a reaction similar to that conducted in Example 147 was carried out. As a result, 0.13 g of N-(trans-4-methylcyclohexyl) -3-[4-(3-carboxypropoxy)-3-methoxyphenyl]propionamide (a compound of the present invention) was obtained as white crystal, which had the following physiochemical properties:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:25]=[CH:24][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH:16](O)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)=[O:8])=[CH:5][CH:4]=1.I>>[N:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[CH2:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[NH:9][C:7](=[O:8])[C:6]1[CH:24]=[CH:25][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1
Reactant: COc1ccc(C(=O)Nc2ccccc2C(O)c2ccccn2)cc1
Agent: I
Product: COc1ccc(C(=O)Nc2ccccc2Cc2ccccn2)cc1

Procedure:
Treatment of 4-methoxy-2'-[hydroxy(2-pyridyl)methyl]benzanilide with hydrogen iodide according to the procedure of Miller, et al., J. Org. Chem., 24, 1364 (1959 ) provides 2'-(2-pyridylmethyl)-p-anisanilide, m.p. 130.5° - 131.5° C. (corr.), from methanol.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.O=S(Cl)Cl.[C:10]([C:12]1[CH:17]=[CH:16][C:15]([C:18](=O)[CH2:19][CH2:20][C:21]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=2)=[CH:14][CH:13]=1)#[N:11]>C(Cl)Cl>[C:10]([C:12]1[CH:13]=[CH:14][C:15]([C:18]([N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)=[CH:19][CH2:20][C:21]2[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=2)=[CH:16][CH:17]=1)#[N:11]
Reactant: c1c[nH]cn1
Reactant: N#Cc1ccc(C(=O)CCc2ccc(F)cc2)cc1
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Product: N#Cc1ccc(C(=CCc2ccc(F)cc2)n2ccnc2)cc1
Reaction time: 0.17 h

Procedure:
Imidazole (0.55 g, 8 mmol) is dissolved in dry tetrahydrofaran. The solution is cooled on icebath and SOCl2 (0.16 ml, 2 mmol) is added dropwise to the cooled solution. The mixture is stirred for 10 min. 1-(4-cyanophenyI)-3-(4-fluorophenyl)-1-propanone (0.34 g, 1.3 mmol) is added and the mixture is stirred in room temperature for 4 days. Methylene chloride is added and the mixture is washed with water. The organic layer is dried and the solvent is evaporated. The residue contains 35% of the product (1H NMR) as a 9:1 mixture of the isomers. The product is purified by flash chromatography (eluent CH2Cl2 -MeOH 99:1).