Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.[I:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH:21]=[C:20]([CH2:22][NH2:23])[CH:19]=[N:18]2)=[CH:13][CH:12]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.O>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[S:6][C:5]([C:7]([NH:23][CH2:22][C:20]2[CH:19]=[N:18][N:17]([C:14]3[CH:15]=[CH:16][C:11]([I:10])=[CH:12][CH:13]=3)[CH:21]=2)=[O:9])=[CH:4][CH:3]=1
Reactant: NCc1cnn(-c2ccc(I)cc2)c1
Reactant: O=C(O)c1ccc(Cl)s1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: O=C(NCc1cnn(-c2ccc(I)cc2)c1)c1ccc(Cl)s1
Temperature: 25 °C
Reaction time: 8 h
Yield: 78.9 %

Procedure:
To a solution of 5-chloro-thiophene-2-carboxylic acid (237 mg, 1.46 mmol), (1-(4-iodophenyl)-1H-pyrazol-4-yl)methanamine (396 mg, 1.32 mmol) and TEA (0.500 mL, 3.59 mmol) in DMF (10 mL), BOP (828 mg, 1.87 mmol) were added. The mixture was stirred at room temperature overnight. H2O and EtOAc were added. The organic phase was separated, washed with 5% NaHCO3, dried over Na2SO4, concentrated in vacuo to give 5-chloro-N-((1-(4-iodophenyl)-1H-pyrazol-4-yl)methyl)thiophene-2-carboxamide (462 mg).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([C:8]2[CH2:12][C:11]([C:17]3[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=3)([C:13]([F:16])([F:15])[F:14])[CH2:10][N:9]=2)[CH:5]=[CH:4][C:3]=1[CH2:25][N:26]1C(=O)C2=CC=CC=C2C1=O.O.NN>C(O)C>[NH2:26][CH2:25][C:3]1[CH:4]=[CH:5][C:6]([C:8]2[CH2:12][C:11]([C:17]3[CH:22]=[C:21]([Cl:23])[CH:20]=[C:19]([Cl:24])[CH:18]=3)([C:13]([F:16])([F:14])[F:15])[CH2:10][N:9]=2)=[CH:7][C:2]=1[Br:1]
Reactant: O=C1c2ccccc2C(=O)N1Cc1ccc(C2=NCC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)cc1Br
Agent: NN
Solvent: O
Solvent: CCO
Product: NCc1ccc(C2=NCC(c3cc(Cl)cc(Cl)c3)(C(F)(F)F)C2)cc1Br
Temperature: 25 °C

Procedure:
To a solution of 0.22 g of N-[2-bromo-4-[4-(3,5-dichlorophenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrole-2-yl]phenylmethyl]phthalimide in 5 mL of ethanol, 0.074 g of hydrazine monohydrate was added and the resultant reaction mixture was stirred while heating the mixture to reflux for 2 hours. After the completion of the reaction, the reaction mixture was left to be cooled down to room temperature and deposited insoluble substances were filtered off, followed by distilling off the solvent under reduced pressure. To the resultant residue, 20 mL of chloroform was added and insoluble substances were filtered off, followed by washing the filtrate with water (20 mL×1). Subsequently, the filtrate was dehydrated and dried over a saturated brine and anhydrous sodium sulfate in this order and the solvent was distilled off under reduced pressure to obtain 0.18 g of the objective substance as a yellow resinoid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22](Cl)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH:24][C:25]1[C:26]([CH3:31])=[N:27][CH:28]=[CH:29][CH:30]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:18]3=[N:19][CH:20]=[N:21][C:22]([O:24][C:25]4[C:26]([CH3:31])=[N:27][CH:28]=[CH:29][CH:30]=4)=[C:17]3[CH:16]=[N:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1ncccc1O
Reactant: CC(C)(C)OC(=O)N1CCC(n2ncc3c(Cl)ncnc32)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1ncccc1Oc1ncnc2c1cnn2C1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 100 °C
Yield: 88.7 %

Procedure:
A mixture of 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 19; 3.00 g, 8.9 mmol), 3-hydroxy-2-methylpyridine (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 1.26 g, 12 mmol), and potassium carbonate (1.59 g, 11.5 mmol) in dimethylformamide (30 mL) was heated at 100° C. overnight. The solvent was evaporated under high vacuum. Water (50 mL) and dichloromethane (50 mL) were added. The layers were separated and the organic layer was washed twice with water and then evaporated to dryness to give 4-[4-(2-methyl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (3.24 g, 89%). A sample of this material (500 mg) was purified by silica gel column chromatography, eluting with 0-75% ethyl acetate/hexanes, to give 4-[4-(2-methyl-pyridin-3-yloxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid tert-butyl ester (381 mg, 10%) as a white powder. 1H NMR (300 MHz, CDCl3) δ 1.49 (s, 9H), 1.97-2.06 (m, 2H), 2.20-2.34 (m, 2H), 2.47 (s, 3H), 2.91-3.05 (m, 2H), 4.26-4.39 (m, 2H), 4.91-5.03 (m, 1H), 7.27-7.29 (m, 1H), 7.50-7.55 (m, 1H), 8.07 (s, 1H), 8.48-8.51 (m, 2H). Mass spectrum MH+=411. HRMS Calcd. For C21H27N6O3 (MH+): 411.2139. Found: 411.2137.
Reaction SMILES: [Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH2:16])[CH:11]=[CH:12][C:13]=1[O:14][CH3:15].[F:17][C:18]1[CH:23]=[CH:22][C:21]([N:24]=[C:25]=[O:26])=[CH:20][CH:19]=1>C(Cl)Cl>[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:16][C:25]([NH:24][C:21]2[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=2)=[O:26])[CH:11]=[CH:12][C:13]=1[O:14][CH3:15]
Reactant: COc1ccc(N)cc1-c1c(Br)cnn1C
Reactant: O=C=Nc1ccc(F)cc1
Solvent: ClCCl
Product: COc1ccc(NC(=O)Nc2ccc(F)cc2)cc1-c1c(Br)cnn1C
Yield: 85.1 %

Procedure:
3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine (2.965 g, 10.5 mmol) was treated with 4-fluorophenyl isocyanate (1.601 g, 1.31 mL, 11.6 mmol, 1.1 equiv.) in CH2Cl2 (20 mL), in a similar manner as described in Example 1.2 to afford Compound 2 (3.755 g, 8.94 mmol, 85%) as a white solid. LCMS m/z (%)=419 (M+H79Br, 99), 421 (M+H81Br, 100). 1H NMR (400 MHz, acetone-d6) δ: 8.49 (broad s, 2H), 7.77 (d, J=9.0 Hz, 1H), 7.50-7.58 (m, 2H), 7.50 (s, 1H), 7.43 (s, 1H), 7.12 (d, J=8.9 Hz, 1H), 6.98-7.06 (m, 2H), 3.81 (s, 3H), 3.68 (s, 3H).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10]([N:13]2[CH2:18][CH2:17][CH:16]([CH2:19][OH:20])[CH2:15][CH2:14]2)(=[O:12])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].O>CS(C)=O.C1COCC1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([N:13]2[CH2:18][CH2:17][CH:16]([CH:19]=[O:20])[CH2:15][CH2:14]2)(=[O:11])=[O:12])=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)N2CCC(CO)CC2)cc1
Solvent: CS(C)=O
Solvent: C1CCOC1
Solvent: O
Product: O=CC1CCN(S(=O)(=O)c2ccc([N+](=O)[O-])cc2)CC1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 92.8 %

Procedure:
A mixture of 1-hydroxy-1,2-benziodooxol-3(1H)-one-1-oxide (IBX) (8.73 g, 3.12 mmol) in DMSO (30 mL) and THF (15 mL) was stirred at room temperature over a period of 20 minutes. In one portion [1-(4-Nitro-benzenesulfonyl)-piperidin-4-yl]-methanol (4.69 g, 15.6 mmol) was added and the solution heated to 50° C. Water was added to the reaction until a white precipitate formed. The reaction mixture was filtered and washed with ethyl acetate. The filtrate was partitioned with ethyl acetate and water. The organic phase was dried (sodium sulfate) and concentrated in vacuo to give 4.32 g of the product as a tan solid
Reaction SMILES: [F:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[Br:15][C:16]1[C:17](Cl)=[C:18]([N+:23]([O-:25])=[O:24])[C:19]([NH2:22])=[N:20][CH:21]=1>CC(O)C.CCN(C(C)C)C(C)C>[Br:15][C:16]1[C:17]([N:10]2[CH2:11][CH2:12][N:7]([CH2:6][C:5]3[CH:13]=[CH:14][C:2]([F:1])=[CH:3][CH:4]=3)[CH2:8][CH2:9]2)=[C:18]([N+:23]([O-:25])=[O:24])[C:19]([NH2:22])=[N:20][CH:21]=1
Reactant: Fc1ccc(CN2CCNCC2)cc1
Reactant: Nc1ncc(Br)c(Cl)c1[N+](=O)[O-]
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: Nc1ncc(Br)c(N2CCN(Cc3ccc(F)cc3)CC2)c1[N+](=O)[O-]
Temperature: 60 °C
Reaction time: 17 h
Yield: 79.1 %

Procedure:
1-(4-Fluorobenzyl)piperazine (0.160 g, 0.81 mmol, 1.05 eq) was suspended in iPrOH (8 mL) and DIPEA (0.72 mL). To this solution, the 5-bromo-4-chloro-3-nitropyridin-2-amine (0.19 g, 0.77 mmol, 1 eq) was added and the reaction mixture was heated and stirred for 17 h at 60° C. The mixture was filtered, washed with iPrOH (3×3 mL), Et2O (2×3 mL) and dried to give the title compound as a bright yellow solid (0.250 g, 75%); 1H-NMR (500 MHz, DMSO-d6): δ 2.43-2.55 (m, 4H, piperazine N(CH2)2), 3.05 (m, 4H, piperazine N(CH2)2), 3.51 (s, 2H, NCH2), 6.96 (br s, 2H, NH2), 7.14 (t, J=9.0 Hz, 2H, ArH), 7.35 (dd, J=8.5, 6.0 Hz, 2H, ArH), 8.15 (s, 1H, pyridine 6-H). LC (Method B)-MS (ESI, m/z): Rt=2.52 min—410/412 [(M+H+), Br isotopic pattern, 100%].
Reaction SMILES: [Cl:1][C:2]1[N:7]=[N:6][C:5]([NH:8][N:9]=[C:10]([C:24]2[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=2)[C:11]2[C:12]([CH2:20][CH:21](O)[CH3:22])=[CH:13][C:14]3[O:18][CH2:17][O:16][C:15]=3[CH:19]=2)=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>CN(C)C=O>[Cl:1][C:2]1[N:7]=[N:6][C:5]([N:8]2[CH:21]([CH3:22])[CH2:20][C:12]3[CH:13]=[C:14]4[O:18][CH2:17][O:16][C:15]4=[CH:19][C:11]=3[C:10]([C:24]3[CH:25]=[CH:26][C:27]([N+:30]([O-:32])=[O:31])=[CH:28][CH:29]=3)=[N:9]2)=[CH:4][CH:3]=1
Reactant: CC(O)Cc1cc2c(cc1C(=NNc1ccc(Cl)nn1)c1ccc([N+](=O)[O-])cc1)OCO2
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: CC1Cc2cc3c(cc2C(c2ccc([N+](=O)[O-])cc2)=NN1c1ccc(Cl)nn1)OCO3
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 41.5 %

Procedure:
A mixture of 0.3 g (0.66 mmol) of the compound prepared in Step A, 10 ml of dimethylformamide and 0.34 g (1.30 mmol) of triphenyiphosphine was stirred at room temperature for 5 min, then 0.20 ml (1.27 mmol) of diethyl azodicarboxylate was added and stirring was continued for 24 h. After dilution with sodium chloride solution the precipitated product was filtered off, dried and purified by column chromatography using silica gel (MN Kieselgel 60) as adsorbent and a mixture of chloroform-methanol (99:1) as eluent. The residue obtained on concentration was crystallized by refluxing in ethanol to yield 0.12 g (42%) of the title compound; Mp.: 254-255° C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[CH3:10])[C:5]#[N:6].[Br:11]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.CC(N=NC(C#N)(C)C)(C#N)C>[Br:11][CH2:10][C:9]1[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[CH:3][C:2]=1[F:1]
Reactant: Cc1ccc(C#N)cc1F
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: N#Cc1ccc(CBr)c(F)c1
Yield: 11.1 %

Procedure:
To a solution of 3-fluoro-4-methylbenzonitrile (5.0 g, 0.23 mol) in 100 mL of carbon tetrachloride was added N-bromosuccinimide (4.97 g, 0.28 mol) and AIBN (100 mg, 0.61 mmol) and the mixture was refluxed for six hours. The reaction was cooled and filtered. The filtrate was washed with water, dried over magnesium sulfate, filtered and the solvents were removed under vacuum to afford 5.44 g of the title compound as an off-white solid. 1H NMR indicated the presence of 20% starting material. 1H NMR (400 MHz, CDCl3) for the title compound: δ 7.54-7.30 (m, 3H), 4.83 (s, 2H).
Reaction SMILES: [CH:1]1([CH2:7][N:8]2[C:16](=[O:17])[C:15]3[N:14]=[C:13]([C:18]4[CH:26]=[CH:25][CH:24]=[CH:23][C:19]=4C(O)=O)[NH:12][C:11]=3[N:10]([CH2:27][CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]3)[C:9]2=[O:34])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(OC(=O)C(Br)C(C1C=CC([C:48]2[NH:49][C:50]3N(CC4CCCCC4)C(=O)N(CC4CCCCC4)C(=O)[C:55]=3[N:56]=2)=CC=1)Br)C>>[CH:1]1([CH2:7][N:8]2[C:16](=[O:17])[C:15]3[N:14]=[C:13]([C:18]4[CH:19]=[CH:23][CH:24]=[C:25](/[CH:11]=[CH:15]/[C:16]([N:49]5[CH:50]=[CH:55][N:56]=[CH:48]5)=[O:17])[CH:26]=4)[NH:12][C:11]=3[N:10]([CH2:27][CH:28]3[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]3)[C:9]2=[O:34])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CCOC(=O)C(Br)C(Br)c1ccc(-c2nc3c(=O)n(CC4CCCCC4)c(=O)n(CC4CCCCC4)c3[nH]2)cc1
Reactant: O=C(O)c1ccccc1-c1nc2c(=O)n(CC3CCCCC3)c(=O)n(CC3CCCCC3)c2[nH]1
Product: O=C(/C=C/c1cccc(-c2nc3c(=O)n(CC4CCCCC4)c(=O)n(CC4CCCCC4)c3[nH]2)c1)n1ccnc1
Reaction time: 18 h

Procedure:
A slurry of (E)-3-[(1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzoic acid (from part (a) of this example, 0.500 g) in anhydrous N,N-dimethylfonnamide (10 mL) was heated briefly to near reflux under nitrogen. N,N′-Carbonyldiimidazole (Aldrich, 0.213 g) was added to the pale yellow slurry, which thinned and turned orange as a gas evolved. Within minutes the slurry turned bright yellow and yellow solid precipitated. The mixture was stirred for 18 h, diluted with dichloromethane (30 mL), and filtered. The solid was washed with dichloromethane (30 mL) and dried at 40° C. to provide (E)-1,3-bis(cyclohexylmethyl)-8-[3-(2-(1H-imidazol-1-ylcarbonyl)vinyl)phenyl]-9H-purin-2,6(1H,3H)-dione as a yellow powder (0.46 g). A mixture of this solid (0.45 g), nonaethylene glycol monomethyl ether, (from part (a) of example 10, 0.393 g) and anhydrous potassium carbonate (0.242 g) in acetonitrile (10 mL) was stirred at reflux for 20 h. Chloroform (50 mL) was added and the solution was washed with 1N HCl, (20 mL). The organic layer was washed with brine, dried (magnesium sulfate), and chromatographed on silica gel. Elution with 10% methanolchloroform evaporation of solvents gave (E)-3-[1,3-bis(cyclohexylmethyl)-1,2,3,6-tetrahydro-2,6-dioxo-9H-purin-8-yl]benzoic acid nonaethylene glycol methyl ether ester as a waxy white solid (0.262 g, 38%); 1H-NMR (DMSO-d6)6: 8.79 (s) and 8.43 (d, J=7.9), 8.11 (d, J=8.0), and 7.57 (m, each 1, C6H4), 4.50 (m, 2, CH2O), 3.99 (d,J=7.1, 2, CH2N), 3.83 (m, 4, CH2N and CH2O), 3.70-3.40 (m, 32, 16 CH2), 3.28 (s, 3, CH3), 2.1-1.6 and 1.4-1.0 (both m, 22, cyclohexyl CH2 and CH).
Reaction SMILES: Cl.[NH2:2][OH:3].CC(C)([O-])C.[Na+].[CH2:10]([C:14]1[CH:19]=[CH:18][C:17]([CH:20]([CH3:23])[C:21]#[N:22])=[CH:16][CH:15]=1)[CH:11]([CH3:13])[CH3:12]>C(O)C>[CH2:10]([C:14]1[CH:15]=[CH:16][C:17]([CH:20]([CH3:23])[C:21]([NH:2][OH:3])=[NH:22])=[CH:18][CH:19]=1)[CH:11]([CH3:13])[CH3:12]
Reactant: NO
Reactant: CC(C)Cc1ccc(C(C)C#N)cc1
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CC(C)Cc1ccc(C(C)C(=N)NO)cc1
Temperature: 25 °C
Yield: 70 %

Procedure:
A mixture of hydroxylamine hydrochloride (0.38 g, 5.32 mmol) and sodium tert-butoxide (0.5 g, 5.28 mmol) in ethyl alcohol (10 mL) is stirred at r.t. for 15′; the precipitate is filtered off and the mother liquors are added dropwise to a solution of 2-(4-isobutylphenyl)propionitrile (0.11 g, 0.49 mmol) in absolute ethyl alcohol (3 mL). The resulting solution is refluxed 18 h. After cooling at r.t. the solvents are evaporated under reduced pressure and the crude residue is diluted in trichloromethane (25 mL), washed with 5% solution of citric acid (2×15 mL), then with a saturated solution of NaCl (2×15 mL), dried over Na2SO4 and evaporated under vacuum to give 2-(4-isobutylphenyl)-N-hydroxy-propionamidine isolated as white solid after crystallisation from n-hexane (0.075 g, 0.34 mmol). Yield 70%. m.p. 75-78° C. 1H-NMR (CDCl3): δ 7.25 (d, 2H, J=7 Hz); 7.12 (d, 2H, J=7 Hz); 5.030 (bs, 1H, NH); 4.35 (bs, 2H, NH—OH); 3.58 (q, 1H, J=8 Hz); 2.48 (d, 2H, J=8 Hz); 1.87 (m, 1H); 1.50 (d, 3H, J=8 Hz); 0.92 (d, 6H, J=8 Hz).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]([C:11]2[C:16]([CH2:17][CH3:18])=[C:15]([O:19]C)[N:14]=[C:13]([O:21]C)[N:12]=2)=[O:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1>Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([Cl:8])[CH:7]=1)[C:9]([C:11]1[NH:12][C:13](=[O:21])[NH:14][C:15](=[O:19])[C:16]=1[CH2:17][CH3:18])=[O:10]
Reactant: CCc1c(OC)nc(OC)nc1C(=O)c1cc(Cl)cc(Cl)c1
Agent: Cl
Product: CCc1c(C(=O)c2cc(Cl)cc(Cl)c2)[nH]c(=O)[nH]c1=O
Temperature: 25 °C
Yield: 93.5 %

Procedure:
Compound (63) (1.26 g, 3.69 mmol) was refluxed with conc. HCl (20 ml) for 5 hr. After cooling to room temperature, the white precipitate was collected by filtration, washed with cold water, and dried in high vacuo to afford 1.08 g (93%) of the title compound as a white solid. m.p. 242-243° C.; 1H NMR (200 MHz, CDCl3/CD3OD) δ 0.90 (3H, t, J=7.5 Hz), 2.07 (2H, q, J=7.5 Hz), 7.59 (1H, t, J=1.8 Hz), 7.67 (2H, d, J=1.8 Hz); HRMS (EI) Calcd. 312.0068, Found 312.0049.
Reaction SMILES: [CH:1](=O)[CH2:2]CCCC.C(=O)CCCCCC.[CH2:16]([C:19]([CH2:24][OH:25])([CH2:22][OH:23])[CH2:20][OH:21])[CH2:17][CH3:18]>>[CH2:16]([C:19]([CH2:24][OH:25])([CH2:22][OH:23])[CH2:20][OH:21])[CH2:17][CH2:18][CH2:1][CH3:2]
Reactant: CCCC(CO)(CO)CO
Reactant: CCCCCC=O
Solvent: CCCCCCC=O
Product: CCCCCC(CO)(CO)CO

Procedure:
2-n-Butyl-2-hydroxmethyl-propan-1,3-diol and 2-n-pentyl-2-hydroxymethyl-propan-1,3-diol were prepared from n-hexanal and n-heptanal respectively in a manner analogous to that described for the synthesis of 2-n-propyl-2-hydroxymethyl-propan-1,3-diol.
Reaction SMILES: [Cl:1][C:2]1[C:7]([C:8]2[NH:12][CH:11]=[C:10]([CH:13]=[O:14])[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.[H-].[Na+].[C:17]([C:19]1[CH:20]=[C:21]([S:25](Cl)(=[O:27])=[O:26])[CH:22]=[CH:23][CH:24]=1)#[N:18]>O1CCCC1.C(=O)([O-])O.[Na+]>[Cl:1][C:2]1[C:7]([C:8]2[N:12]([S:25]([C:21]3[CH:20]=[C:19]([CH:24]=[CH:23][CH:22]=3)[C:17]#[N:18])(=[O:27])=[O:26])[CH:11]=[C:10]([CH:13]=[O:14])[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: N#Cc1cccc(S(=O)(=O)Cl)c1
Reactant: O=Cc1c[nH]c(-c2cccnc2Cl)c1
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: N#Cc1cccc(S(=O)(=O)n2cc(C=O)cc2-c2cccnc2Cl)c1
Reaction time: 0.17 h
Yield: 75.8 %

Procedure:
To a solution of 5-(2-chloropyridin-3-yl)-1H-pyrrole-3-carbaldehyde (110 mg) in tetrahydrofuran (11 mL) was added sodium hydride (60% in oil, 64 mg) at room temperature and the mixture was stirred for 10 min. 3-Cyanobenzenesulfonyl chloride (215 mg) was added and the mixture was further stirred for 15 min. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The obtained extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from diethyl ether to give the title compound as colorless crystals (yield 150 mg, 76%).
Reaction SMILES: [CH2:1]([C:8]#[N:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:10][C:11]1[CH:23]=[CH:22][C:14]([CH2:15][CH2:16]CS([O-])(=O)=O)=[CH:13][CH:12]=1.C1(C)C=CC=CC=1.[OH-].[Na+]>O.CS(C)=O>[Cl:10][C:11]1[CH:23]=[CH:22][C:14]([CH2:15][CH2:16][CH:1]([C:8]#[N:9])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:13][CH:12]=1
Reactant: O=S(=O)([O-])CCCc1ccc(Cl)cc1
Reactant: N#CCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: CS(C)=O
Solvent: O
Product: N#CC(CCc1ccc(Cl)cc1)c1ccccc1
Temperature: 5 °C
Reaction time: 3 h
Yield: 79.8 %

Procedure:
This product was also obtained by charging a reaction vessel with 58.6 gm of benzylcyanide (0.5 mole), 116.8 gm of 4-chlorophenethylmethanesulfonate (0.5 mole), 500 ml of toluene and 500 ml of dimethylsulfoxide. The mixture was cooled to about 5° C. and 50% sodium hydroxide was added slowly with rapid mixing while maintaining the temperature at about 5°-10° C. After the addition of the sodium hydroxide (about 1.5 hours), the mixture was allowed to warm to room temperature and then stirred for another three hours. One liter of water was added to the mixture and it was transferred to a separatory funnel where it was extracted with ether; the combined ether extracts were sequentially washed with 5% hydrochloric acid, water and brine. The liquid obtained after solvent removal was distilled to obtain 102 gm of 3-(4-chlorophenyl)-1-cyano1-phenylpropane.
Reaction SMILES: [C:1]1([CH:7]([O:14][C:15]([C:17]2[N:18]3[C@H:21]([S:22][CH2:23][C:24]=2[CH2:25][S:26][C:27]2[S:37][C:30]4=[N:31][C:32]([CH3:36])=[CH:33][C:34](=[O:35])[N:29]4[N:28]=2)[C@H:20]([NH:38][C:39](=[O:68])/[C:40](/[C:43]2[N:44]=[C:45]([C:49]([C:62]4[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=4)([C:56]4[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=4)[C:50]4[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=4)[S:46][C:47]=2[NH2:48])=[N:41]\[OH:42])[C:19]3=[O:69])=[O:16])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:76][CH2:77][C:78]([O:80][C:81]1[C:89]([O:90][C:91](=[O:94])[CH2:92][Cl:93])=[CH:88][C:84]([C:85](Cl)=[O:86])=[C:83]([CH3:95])[CH:82]=1)=[O:79]>ClCCl>[C:1]1([CH:7]([O:14][C:15]([C:17]2[N:18]3[C@H:21]([S:22][CH2:23][C:24]=2[CH2:25][S:26][C:27]2[S:37][C:30]4=[N:31][C:32]([CH3:36])=[CH:33][C:34](=[O:35])[N:29]4[N:28]=2)[C@H:20]([NH:38][C:39](=[O:68])/[C:40](/[C:43]2[N:44]=[C:45]([C:49]([C:56]4[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=4)([C:50]4[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=4)[C:62]4[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=4)[S:46][C:47]=2[NH2:48])=[N:41]\[O:42][C:85](=[O:86])[C:84]2[CH:88]=[C:89]([O:90][C:91](=[O:94])[CH2:92][Cl:93])[C:81]([O:80][C:78](=[O:79])[CH2:77][Cl:76])=[CH:82][C:83]=2[CH3:95])[C:19]3=[O:69])=[O:16])[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Cc1cc(=O)n2nc(SCC3=C(C(=O)OC(c4ccccc4)c4ccccc4)N4C(=O)[C@@H](NC(=O)/C(=N\O)c5nc(C(c6ccccc6)(c6ccccc6)c6ccccc6)sc5N)[C@H]4SC3)sc2n1
Reactant: Cc1cc(OC(=O)CCl)c(OC(=O)CCl)cc1C(=O)Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Product: Cc1cc(=O)n2nc(SCC3=C(C(=O)OC(c4ccccc4)c4ccccc4)N4C(=O)[C@@H](NC(=O)/C(=N\OC(=O)c5cc(OC(=O)CCl)c(OC(=O)CCl)cc5C)c5nc(C(c6ccccc6)(c6ccccc6)c6ccccc6)sc5N)[C@H]4SC3)sc2n1
Temperature: 0 °C
Reaction time: 1 h
Yield: 60 %

Procedure:
To an ice-cooled solution of the product obtained in Step 4 (0.6 g) in dry dichloromethane (15 ml) was added potassium carbonate (0.1 g) at once, followed by dropwise addition of a solution of 4,5-bis(chloroacetoxy)-2-methylbenzoyl chloride (0.25 g) in dry dichloromethane (10 ml). The mixture was stirred under ice cooling for one hour and then at room temperature for an additional two hours. After filtering off the insoluble matters, the filtrate was washed with water and with brine, and dried over anhydrous sodium sulfate. The dried solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography, giving 0.47 g of the objective compound.
Reaction SMILES: [NH2:1][CH:2]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:6]2[CH:15]=[CH:16][CH:17]=[CH:18][C:5]=2[N:4]([CH3:19])[C:3]1=[O:20].[F:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]=[C:29]=[O:30])=[CH:24][CH:23]=1>O1CCCC1>[CH3:19][N:4]1[C:5]2[CH:18]=[CH:17][CH:16]=[CH:15][C:6]=2[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:8][CH:2]([NH:1][C:29]([NH:28][C:25]2[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=2)=[O:30])[C:3]1=[O:20]
Reactant: CN1C(=O)C(N)N=C(c2ccccc2)c2ccccc21
Reactant: O=C=Nc1ccc(F)cc1
Solvent: C1CCOC1
Product: CN1C(=O)C(NC(=O)Nc2ccc(F)cc2)N=C(c2ccccc2)c2ccccc21
Reaction time: 8 h

Procedure:
Equimolar amounts of 3(R,S)-amino-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one and 4-fluorophenylisocyanate were mixed in 8 ml of dry tetrahydrofuran at room temperature. The reaction mixture was allowed to stand for 8 hours and was then filtered. The collected solids were washed with tetrahydrofuran and dried in vacuo over P2O5 to give the analytical product: m.p. 269°-270° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([S:8]([C:11]2[CH:16]=[CH:15][C:14]([N+:17]([O-])=O)=[CH:13][CH:12]=2)(=[O:10])=[O:9])[CH:5]=[C:4]([CH3:20])[N:3]=1.[NH4+].[Cl-].C(OCC)(=O)C>CO.O.[Fe]>[Br:1][C:2]1[CH:7]=[C:6]([S:8]([C:11]2[CH:12]=[CH:13][C:14]([NH2:17])=[CH:15][CH:16]=2)(=[O:9])=[O:10])[CH:5]=[C:4]([CH3:20])[N:3]=1
Reactant: Cc1cc(S(=O)(=O)c2ccc([N+](=O)[O-])cc2)cc(Br)n1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CO
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1cc(S(=O)(=O)c2ccc(N)cc2)cc(Br)n1
Yield: 97.5 %

Procedure:
0.15 g (0.00042 mol) of 2-bromo-6-methyl-4-(4-nitrobenzenesulphonyl)-pyridine was dissolved in 10 ml of methanol, treated with 0.18 g of iron powder and a solution of 0.18 g of NH4Cl in 5 ml of water and heated at reflux for 1 hr. Thereafter, the reaction mixture was poured into a mixture of ethyl acetate and water, suction filtered and the organic phase was extracted with water and sat. sodium chloride solution and dried over MgSO4. After removal of the solvent the residue was dried in a high vacuum. There was obtained 0.134 g (98%) of 4-(2-bromo-6-methylpyridine-4-sulphonyl)-phenylamine as yellowish crystals; m.p.: 189-191° C.