Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([O:13][C:14]1[CH:18]=[C:17]([N:19]2[C:27]3[CH:26]=[C:25]([CH2:28][OH:29])[N:24]=[CH:23][C:22]=3[N:21]=[CH:20]2)[S:16][C:15]=1[C:30]([NH2:32])=[O:31])[C:9]([F:12])([F:11])[F:10].[CH3:33][S:34](Cl)(=[O:36])=[O:35].C(N(CC)CC)C>ClCCl>[CH3:33][S:34]([O:29][CH2:28][C:25]1[N:24]=[CH:23][C:22]2[N:21]=[CH:20][N:19]([C:17]3[S:16][C:15]([C:30](=[O:31])[NH2:32])=[C:14]([O:13][CH:8]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[Cl:1])[C:9]([F:12])([F:11])[F:10])[CH:18]=3)[C:27]=2[CH:26]=1)(=[O:36])=[O:35]
Reactant: NC(=O)c1sc(-n2cnc3cnc(CO)cc32)cc1OC(c1ccccc1Cl)C(F)(F)F
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCc1cc2c(cn1)ncn2-c1cc(OC(c2ccccc2Cl)C(F)(F)F)c(C(N)=O)s1

Procedure:
In a similar manner as described for example 49 (step 1), 170 mg of 3-[1-(2-chlorophenyl)-2,2,2-trifluoroethoxy]-5-[6-(hydroxymethyl)-1H-imidazo[4,5-c]pyridin-1-yl]thiophene-2-carboxamide, 76.7 mg of methanesulfonyl chloride, and 70.8 mg of triethylamine in 3 ml dichloromethane give (1-{5-carbamoyl-4-[1-(2-chlorophenyl)-2,2,2-trifluoroethoxy]-2-thienyl}-1H-imidazo[4,5-c]pyridin-6-yl)methyl methanesulfonate as crude material that is used for step 2 without further purification.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:19]=[C:20]([F:33])[C:21]=1[O:22][Si:23]([CH:30]([CH3:32])[CH3:31])([CH:27]([CH3:29])[CH3:28])[CH:24]([CH3:26])[CH3:25])[CH2:5][CH:6]([CH2:17][OH:18])[CH2:7][CH2:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][CH:10]=1.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([CH:19]=[C:20]([F:33])[C:21]=1[O:22][Si:23]([CH:24]([CH3:26])[CH3:25])([CH:27]([CH3:29])[CH3:28])[CH:30]([CH3:31])[CH3:32])[CH2:5][CH:6]([CH:17]=[O:18])[CH2:7][CH2:8][C:9]1[CH:10]=[CH:11][C:12]([C:13]#[N:14])=[CH:15][CH:16]=1
Reactant: CC(C)[Si](Oc1c(F)cc(CC(CO)CCc2ccc(C#N)cc2)cc1F)(C(C)C)C(C)C
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: CC(C)[Si](Oc1c(F)cc(CC(C=O)CCc2ccc(C#N)cc2)cc1F)(C(C)C)C(C)C
Temperature: 25 °C
Reaction time: 12 h

Procedure:
A solution of 750 mg (1.58 mmol) of 4-[3-(3,5-difluoro-4-triisopropylsilanyloxybenzyl)-4-hydroxybutyl]benzonitrile in 9 ml of dichloromethane is mixed with 409 mg (1.9 mmol) of pyridinium chlorochromate (PCC) and stirred at room temperature for 12 h. After conversion is complete, about 10 g of silica gel are added, and the solvent is removed in vacuo to dryness. The residue is purified by flash chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 10:1→5:1→2:1). 493 mg (64% of theory) of a colorless solid are obtained.
Reaction SMILES: [CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@H:19]([C:29](O)=[O:30])[CH2:20][O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.[NH2:57][CH2:58][CH2:59][CH2:60][CH2:61][N:62]([CH2:75][C:76]1[CH:81]=[CH:80][CH:79]=[CH:78][CH:77]=1)[CH2:63][CH2:64][C@H:65]([NH:67][C:68](=[O:74])[O:69][C:70]([CH3:73])([CH3:72])[CH3:71])[CH3:66]>ClCCl.C(OCC)(=O)C>[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16]([NH:18][C@@H:19]([CH2:20][O:21][CH2:22][C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:29](=[O:30])[NH:57][CH2:58][CH2:59][CH2:60][CH2:61][N:62]([CH2:75][C:76]3[CH:77]=[CH:78][CH:79]=[CH:80][CH:81]=3)[CH2:63][CH2:64][C@@H:65]([CH3:66])[NH:67][C:68]([O:69][C:70]([CH3:73])([CH3:71])[CH3:72])=[O:74])=[O:17])[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1
Reactant: O=C(N[C@@H](COCc1ccccc1)C(=O)O)OCC1c2ccccc2-c2ccccc21
Reactant: C[C@H](CCN(CCCCN)Cc1ccccc1)NC(=O)OC(C)(C)C
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: C[C@H](CCN(CCCCNC(=O)[C@H](COCc1ccccc1)NC(=O)OCC1c2ccccc2-c2ccccc21)Cc1ccccc1)NC(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 96.9 %

Procedure:
1.71 g (4.1.10-3 mol) of N-[(9H-fluoren-9-yl)methoxycarbonyl]-O-phenylmethyl-(L)-serine are dissolved in 60 ml of dichloromethane. The solution is cooled to 0° C. and a solution of 0.55 g (4.10-3 mol) of HOBT and 1.54 g (7.5.10-3 mol) of DCC in 20 ml of dichloromethane is added. The mixture is stirred for 0.5 hour, 1.30 g (3.72.10-3 mol) of N-[3-[(4-aminobutyl)(phenylmethyl)amino]-1-(R)-methylpropyl]carbamic acid, 1, 1-dimethylethyl ester are then added and the reaction mixture is stirred at room temperature for 16 hours. The solvent is removed under reduced pressure and the residue is purified by chromatography on silica gel using an ethyl acetate/methylcyclohexane mixture (1/1 v/v) and then pure ethyl acetate as the eluent to give 2.7 g of the expected product in the form of a white crystalline solid (yield=96%).
Reaction SMILES: [SH:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[OH-].[K+].[CH2:11]1[O:19][CH:12]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Cl>O>[OH:19][CH:12]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:11][S:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1
Reactant: c1ccc(C2CO2)cc1
Reactant: Oc1ccc(S)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: Oc1ccc(SCC(O)c2ccccc2)cc1
Temperature: 120 °C

Procedure:
4-Mercaptophenol (63 grams) and 0.5 gram of KOH were combined in a flask equipped with an agitator, water condenser and thermometer. The combination was heated to 120° C. under nitrogen. Styrene oxide (66 grams) was added dropwise at 100° C. to 135° C. The combination was neutralized with one millimeter of hydrochloric acid and the volatiles stripped off to a pot temperature of 170° C. at 28 millimeters of mercury. The weight of product was 131 grams.
Reaction SMILES: [CH2:1]([CH:3]1[C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH2:6][CH2:5][NH:4]1)[CH3:2].[CH3:12][N:13]=[C:14]=[O:15]>O1CCOCC1.C(OCC)(=O)C>[CH2:1]([CH:3]1[C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH2:6][CH2:5][N:4]1[C:14](=[O:15])[NH:13][CH3:12])[CH3:2]
Reactant: CN=C=O
Reactant: CCC1NCCc2[nH]cnc21
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: CCC1c2nc[nH]c2CCN1C(=O)NC

Procedure:
A solution of 1.51 g of 4-ethyl-4,5,6,7-tetrahydro-imidazo-[4,5-c]-pyridine and 2.28 g of methyl isocyanate in 20 ml of dry dioxane is refluxed for 1.5 h. The solution is cooled and filtered. The solid collected is dissolved in 30 ml of methanol and treated with 7 ml of 2N sodium hydroxide for 2 h at room temperature. After neutralization the solution is extracted with chloroform. Evaporation of the solvent leaves a residue that is taken up in ethyl acetate. 1.05 g of the title compound, m.p. 240°, are collected.
Reaction SMILES: [CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH2:26][CH3:27])[CH2:23][CH2:22][C:21]([C:28]([NH:30][C:31]4[CH:36]=[CH:35][C:34]([S:37][C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=5)=[CH:33][CH:32]=4)=[O:29])=[CH:20][C:19]=3[CH:44]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].ClC1C=CC=C(C(OO)=[O:53])C=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)Cl>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH2:26][CH3:27])[CH2:23][CH2:22][C:21]([C:28]([NH:30][C:31]4[CH:32]=[CH:33][C:34]([S:37]([C:38]5[CH:43]=[CH:42][CH:41]=[CH:40][N:39]=5)=[O:53])=[CH:35][CH:36]=4)=[O:29])=[CH:20][C:19]=3[CH:44]=2)=[CH:13][CH:14]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(Sc4ccccn4)cc2)CCN3CCC)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: CCCCOCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(S(=O)c4ccccn4)cc2)CCN3CCC)cc1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 19.5 %

Procedure:
7-[4-(2-butoxyethoxy)phenyl]-1-propyl-N-[4-(2-pyridinylsulfanyl)phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (0.15 g) was dissolved in methylene chloride (7.5 ml), m-chloroperbenzoic acid (95 mg) was added to the solution at 0° C., and the mixture was stirred for 15 minutes at 0° C. To the mixture was m-chloroperbenzoic acid (95 mg) was added, and the mixture was stirred for 15 minutes. The reaction mixture was added to an aqueous solution of saturated sodium thiosulfate, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure, and the obtained residue was purified by silica gel column chromatography, to give 7-[4-(2-butoxyethoxy)phenyl]-1-propyl-N-[4-(2-pyridinylsulfinyl)phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 183) (30 mg).
Reaction SMILES: O1CCOCC1.[C:7]([O:11][C:12](=[O:39])[N:13]([C@@H:27]([C:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=[CH:31][CH:30]=1)[CH3:28])[CH2:14][CH:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH:16]1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([CH3:10])([CH3:9])[CH3:8].I[C:41]1[CH:42]=[C:43]([CH:49]=[CH:50][CH:51]=1)[C:44]([O:46][CH2:47][CH3:48])=[O:45].C(=O)([O-])[O-].[Cs+].[Cs+]>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].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1.C(OCC)(=O)C.C(O)(C)(C)C>[C:7]([O:11][C:12]([N:13]([CH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:41]2[CH:42]=[C:43]([CH:49]=[CH:50][CH:51]=2)[C:44]([O:46][CH2:47][CH3:48])=[O:45])[CH2:17][CH:16]1[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)[C@@H:27]([C:29]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=[CH:31][CH:30]=1)[CH3:28])=[O:39])([CH3:8])([CH3:9])[CH3:10]
Reactant: CCOC(=O)c1cccc(I)c1
Reactant: C[C@H](c1cccc2ccccc12)N(CC1CCNCC1c1ccccc1)C(=O)OC(C)(C)C
Agent: [Pd]
Agent: CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: CC(C)(C)O
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CCOC(=O)c1cccc(N2CCC(CN(C(=O)OC(C)(C)C)[C@H](C)c3cccc4ccccc34)C(c3ccccc3)C2)c1
Temperature: 100 °C
Reaction time: 8 h
Yield: 81 %

Procedure:
To a mixture of 2.3 mg of tris(dibenzylideneacetone)dipalladium(0), 1.9 mg of 2-(dicyclohexylphosphino)-2′-(dimethylamino)biphenyl, and 0.5 mL of 1,4-dioxane were added 100 mg of tert-butyl[(1R)-1-(1-naphthyl)ethyl][(3-phenylpiperidin-4-yl)methyl]carbamate, 83.8 mg of ethyl 3-iodobenzoate, 105 mg of cesium carbonate, 1.0 mL of 1,4-dioxane, and 1.5 mL of t-butanol, followed by stirring at 100° C. overnight. After cooling to room temperature, to the reaction mixture was added ethyl acetate, the insolubles were removed, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 108 mg of ethyl 3-[4-({(tert-butoxycarbonyl)[(1R)-1-(1-naphthyl)ethyl]amino}methyl)-3-phenylpiperidin-1-yl]benzoate as a pale yellow foamy substance. ESI+: 593
Reaction SMILES: [C:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:11]([CH3:12])[C:10](=[O:13])[N:9]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[Cl:22])[C:8]=2[CH:23]=1)([OH:3])=O.[CH2:24]([S:28]([NH2:31])(=[O:30])=[O:29])[CH2:25][CH2:26][CH3:27].C1CCN2C(=NCCC2)CC1>CN(C)C=O>[CH2:24]([S:28]([NH:31][C:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:11]([CH3:12])[C:10](=[O:13])[N:9]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[Cl:22])[C:8]=2[CH:23]=1)=[O:3])(=[O:30])=[O:29])[CH2:25][CH2:26][CH3:27]
Reactant: CCCCS(N)(=O)=O
Reactant: Cn1c(=O)n(Cc2ccc(Cl)cc2Cl)c2cc(C(=O)O)ccc21
Solvent: CN(C)C=O
Solvent: C1CCC2=NCCCN2CC1
Product: CCCCS(=O)(=O)NC(=O)c1ccc2c(c1)n(Cc1ccc(Cl)cc1Cl)c(=O)n2C
Temperature: 25 °C
Reaction time: 1 h
Yield: 29.2 %

Procedure:
In the same manner as in Example 1, N,N′-carbonyldiimidazole (0.290 g) was added to a mixture of 6-carboxy-1-(2,4-dichlorobenzyl)-3-methyl-2-benzimidazolone (0.314 g) and N,N-dimethylformamide (9 ml), and the mixture was stirred at room temperature for 1 hr. 1-n-Butanesulfonamide (0.246 g) and DBU (0.273 g) were added and the mixture was stirred at 100° C. for 16 hr. The solvent was evaporated and the resulting mixture was extracted with chloroform and water. The organic layer was concentrated and the residue was purified by preparative thin layer chromatography to give 6-(1-n-butanesulfonylcarbamoyl)-1-(2,4-dichlorobenzyl)-3-methyl-2-benzimidazolone (0.123 g).
Reaction SMILES: [C:1]([C:3](=[C:7]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([CH:17]([CH3:19])[CH3:18])=[CH:13][CH:12]=1)SC)[C:4]([NH2:6])=[O:5])#[N:2].O.[NH2:21][NH2:22]>C(O)C>[NH2:2][C:1]1[NH:22][N:21]=[C:7]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH:17]([CH3:19])[CH3:18])=[CH:13][CH:12]=2)[C:3]=1[C:4]([NH2:6])=[O:5]
Reactant: CSC(Nc1ccc(C(C)C)cc1)=C(C#N)C(N)=O
Reactant: NN
Solvent: CCO
Solvent: O
Product: CC(C)c1ccc(Nc2n[nH]c(N)c2C(N)=O)cc1
Temperature: 75 °C
Yield: 66 %

Procedure:
2-cyano-3-((4-isopropylphenyl)amino)-3-(methylthio)acrylamide (1.360 g) was suspended in 15 mL of ethanol and hydrazine hydrate (360 μL, 1.5 eq.) was added drop wise to the reaction. Reaction was then heated at 75° C. until the starting material was no longer present and confirmed via HPLC. Once starting material was absent (18 hrs), reaction was brought to room temperature and filtered to obtain 5-amino-3-((4-isopropylphenyl)amino)-1H-pyrazole-4-carboxamide as an off white to yellow powder. The product was allowed to dry under vacuum for 1 hr (850 mg, 66% yield).
Reaction SMILES: [OH:1][C@@H:2]([C@H:4]1[C:32](=[O:33])[N:6]2[C:7]([C:19]([O:21]CC3C=CC([N+]([O-])=O)=CC=3)=[O:20])=[C:8]([C:11]3[S:15][C:14]4=[CH:16][N:17]=[CH:18][N:13]4[CH:12]=3)[C@H:9]([CH3:10])[C@H:5]12)[CH3:3].P([O-])([O-])([O-])=O>C1COCC1.[Pd]>[OH:1][C@@H:2]([C@H:4]1[C:32](=[O:33])[N:6]2[C:7]([C:19]([OH:21])=[O:20])=[C:8]([C:11]3[S:15][C:14]4=[CH:16][N:17]=[CH:18][N:13]4[CH:12]=3)[C@H:9]([CH3:10])[C@H:5]12)[CH3:3]
Reactant: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(c3cn4cncc4s3)[C@H](C)[C@H]12
Agent: [Pd]
Agent: O=P([O-])([O-])[O-]
Solvent: C1CCOC1
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)O)=C(c3cn4cncc4s3)[C@H](C)[C@H]12
Temperature: 25 °C
Reaction time: 4 h
Yield: 19.6 %

Procedure:
To a solution of 4.70 g of 4-nitro-benzyl (1S,5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-2-yl)-1-methyl-1-carbapen-2-em-3-carboxylate in 90 ml of THF and 50 ml of 1/15 M phosphate buffer (pH 6.8) was added 7.0 g of 10% Pd-C. The reactor was purged with hydrogen, and the reaction mixture was stirred at room temperature for 4 hours. The catalyst was removed by filtration with Celite, and washed with 300 ml of water and 50 ml of THF. The filtrate was diluted with 200 ml of ethyl acetate and washed with water. The aqueous layer was separated from the filtrate, and concentrated under reduced pressure to a volume of about 300 ml, which was purified by column chromatography on DIAION HP-20. The fraction containing the aimed product was concentrated under reduced pressure, crystallized from 12 ml of water to give 656 mg of the title compound.
Reaction SMILES: C([O:5][C:6](=[O:21])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:20])[CH2:13][CH2:14][S:15][C:16]([NH:18][CH3:19])=[S:17])(C)(C)C>C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>[CH3:19][NH:18][C:16]([S:15][CH2:14][CH2:13][C:12]([N:8]1[CH2:9][CH2:10][CH2:11][C@H:7]1[C:6]([OH:21])=[O:5])=[O:20])=[S:17]
Reactant: CNC(=S)SCCC(=O)N1CCC[C@H]1C(=O)OC(C)(C)C
Solvent: COc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: CNC(=S)SCCC(=O)N1CCC[C@H]1C(=O)O

Procedure:
1-[3-[[(Methylamino)thiocarbonyl]thio]propanoyl]-L-proline tertbutyl ester (0.98 g) is dissolved in a mixture of anisole (3.6 ml) and trifluoroacetic acid (7.5 ml). After one hour at room temperature the mixture is concentrated to dryness in vacuo and the residue precipitated from ether-hexane three times. This material is chromatographed on a column of silica gel with a solvent mixture of benzene-acetic acid (75:25) to yield 1-[3-[[(methylamino)thiocarbonyl]thio]propanoyl]-L-proline, Rf = 0.4 [silica gel-benzene:acetic acid (75:25)]. The dicyclohexylammonium salt has m.p. 127°-129°.
Reaction SMILES: [C:1]([C:3]1[C:8]([C:9]2[N:13]([S:14]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=3[F:24])(=[O:16])=[O:15])[CH:12]=[C:11]([CH2:25][N:26](C)[C:27](=O)OC(C)(C)C)[CH:10]=2)=[CH:7][CH:6]=[CH:5][N:4]=1)#[N:2].C(OCC)(=O)C.[ClH:41]>C(OCC)(=O)C.CC(O)C>[ClH:41].[F:24][C:18]1[CH:19]=[C:20]([F:23])[CH:21]=[CH:22][C:17]=1[S:14]([N:13]1[CH:12]=[C:11]([CH2:25][NH:26][CH3:27])[CH:10]=[C:9]1[C:8]1[C:3]([C:1]#[N:2])=[N:4][CH:5]=[CH:6][CH:7]=1)(=[O:16])=[O:15]
Reactant: CN(Cc1cc(-c2cccnc2C#N)n(S(=O)(=O)c2ccc(F)cc2F)c1)C(=O)OC(C)(C)C
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CC(C)O
Product: CNCc1cc(-c2cccnc2C#N)n(S(=O)(=O)c2ccc(F)cc2F)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 74 %

Procedure:
To a solution of tert-butyl ({5-(2-cyanopyridin-3-yl)-1-[(2,4-difluorophenyl)sulfonyl]-1H-pyrrol-3-yl}methyl)methylcarbamate (208 mg) in ethyl acetate (2 mL) and 2-propanol (1 mL) was added 4 mol/L hydrogen chloride-ethyl acetate solution (3 mL), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated under reduced pressure, and the residue was recrystallized from ethanol to give the title compound as a white solid (yield 134 mg, 74%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([SH:8])=[CH:4][C:3]=1[F:9].[H-].[Na+].IC.Cl[CH2:15]Cl>O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH3:15])=[CH:4][C:3]=1[F:9]
Reactant: ClCCl
Reactant: Fc1cc(S)ccc1Br
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: C1CCOC1
Product: CSc1ccc(Br)c(F)c1
Reaction time: 0.08 h
Yield: 86 %

Procedure:
A solution of 4-bromo-3-fluoro-benzenethiol (225 mg, 1.09 mmol) in tetrahydrofuran (3 ml) was cooled to 0° C. Sodium hydride (60% dispersion in mineral oil, 52 mg, 1.31 mmol) was added and the mixture was stirred for 5 minutes. Iodomethane (78 μl, 1.25 mmol) was then added and the mixture was allowed to return to room temperature with stirring over 20 minutes. Dichloromethane (10 ml) was added and the reaction was quenched with 1 M aqueous hydrochloric acid. The layers were separated and the organic layer was washed with water, dried (MgSO4), then concentrated in vacuo. The residue was purified by flash chromatography (Si-PPC, pentane:diethyl ether, gradient 100:0 to 90:10) to afford the title compound as a bright yellow oil (208 mg, 86%). 1H NMR (CDCl3, 400 MHz) 7.43 (1H, dd, J=8.4, 7.2), 7.00 (1H, dd, J=9.4, 2.3), 6.91 (1H, ddd, J=8.4, 2.1, 0.7), 2.48 (3H, s).
Reaction SMILES: [NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:15][C@H:14]([CH2:16][OH:17])[C@@H:13]([N:18]=[N+:19]=[N-:20])[CH2:12]2)=[C:4](Cl)[N:3]=1.[CH2:22]([NH2:26])[CH2:23][CH2:24][CH3:25]>CO>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:15][C@H:14]([CH2:16][OH:17])[C@@H:13]([N:18]=[N+:19]=[N-:20])[CH2:12]2)=[C:4]([NH:26][CH2:22][CH2:23][CH2:24][CH3:25])[N:3]=1
Reactant: [N-]=[N+]=N[C@H]1C[C@H](n2cnc3c(Cl)nc(N)nc32)O[C@@H]1CO
Reactant: CCCCN
Solvent: CO
Product: CCCCNc1nc(N)nc2c1ncn2[C@H]1C[C@H](N=[N+]=[N-])[C@@H](CO)O1
Temperature: 60 °C

Procedure:
2-Amino-9-(3-azido-2,3-dideoxy-β-D-erythro-pentofuranosyl)-6-chloro-9H-purine (Example 3d) (0.40 g, 1.29 mmol) and n-butylamine (Aldrich, #06221JP, 1.28mL, 12.9 mmol) were combined in 25 mL MeOH and placed in a sealed tube. The reaction was heated at 60° C. for 18 hours followed by evaporation of the solvents. Chromatography of the residue on basic alumina eluted with 2% MeOH in CHCl3 gave, after combination and evaporation of appropriate fractions, 0.279 g (0.8 mMol. 62.3%); mp=44°-47°C.
Reaction SMILES: Cl.[NH2:2][OH:3].C(=O)([O-])[O-].[Na+:8].[Na+].[O:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13](=[O:20])[C:12]([C:21](Cl)=[O:22])=[CH:11]1>O.C(Cl)Cl>[O:20]=[C:13]1[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=2[O:10][CH:11]=[C:12]1[C:21]([NH:2][O-:3])=[O:22].[Na+:8]
Reactant: O=C(Cl)c1coc2ccccc2c1=O
Reactant: NO
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: O=C(N[O-])c1coc2ccccc2c1=O

Procedure:
A solution of 8.34 g (0.12 mol) of hydroxylamine hydrochloride in 125 ml of water was mixed with 100 ml of methylenechloride. Solid sodium carbonate (50 g) was added with cooling. With stirring, a solution of 16.5 g (0.079 mol) of chromone-3-carbonylchloride in 250 ml of methylene chloride was added over a period of 5 minutes, keeping the temp. at 15° with ice bath cooling. After 15 minutes reaction time the thick mixture was filtered and washed with 200 ml of ice-water. The damp filter cake was recrystallized from 100 ml of water, wt 1.5 g (8.4%); mp > 300°.
Reaction SMILES: [OH-].[K+].[CH3:3]C1C=CC(S(N(N=O)C)(=O)=O)=CC=1.[N+](=C)=[N-].[OH:20][N:21]1[C:25](=[O:26])[C:24]([CH:28]([CH3:30])[CH3:29])([CH3:27])[N:23]=[C:22]1[C:31]1[CH:39]=[CH:38][CH:37]=[CH:36][C:32]=1[C:33]([OH:35])=[O:34]>C(OCC)(=O)C.C(O)C.CCOCC>[OH:20][N:21]1[C:25](=[O:26])[C:24]([CH:28]([CH3:30])[CH3:29])([CH3:27])[N:23]=[C:22]1[C:31]1[CH:39]=[CH:38][CH:37]=[CH:36][C:32]=1[C:33]([O:35][CH3:3])=[O:34]
Reactant: CC(C)C1(C)N=C(c2ccccc2C(=O)O)N(O)C1=O
Reactant: Cc1ccc(S(=O)(=O)N(C)N=O)cc1
Agent: C=[N+]=[N-]
Agent: [K+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CCO
Solvent: CCOCC
Product: COC(=O)c1ccccc1C1=NC(C)(C(C)C)C(=O)N1O
Reaction time: 0.17 h
Yield: 26 %

Procedure:
A solution of potassium hydroxide (0.19 g, 0.00339 mol) and ethanol is added portionwise to a 0° C. mixture of Diazald® N-methyl-N-nitroso-D-toluenesulfonamide (0.73 g, 0.0034 mol) and ether. The mixture is kept in an ice-bath for 10 minutes then in an water bath for 10 minutes. The diazomethane is distilled into a mixture of o-(1-hydroxy-4-isopropyl-4-methyl-5-oxo-2-imi-dazolin-2-yl)benzoic acid (0.67 g, 0.00243 mol) and ethanol. After 45 minutes the reaction mixture is quenched with acetic acid and concentrated in vacuo to give an oil. The oil is dissolved into ethyl acetate, dried over anhydrous magnesium sulfate and concentrated in vacuo to yield an off-white solid. The solid is chromatographed using silica gel and methylene chloride/ethyl acetate 3:1 as eluent to give the title compound as a white solid (0.18 g, 26%), mp 146°-150° C., identified by IR and NMR spectral analyses.
Reaction SMILES: [CH:1]1([C:5]([OH:7])=[O:6])[CH2:4][CH2:3][CH2:2]1.C1CCC(N=C=NC2CCCCC2)CC1.CS(O[C:28]1[CH:37]=[CH:36][C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:38](=[NH:40])[NH2:39])[CH:34]=2)[CH:29]=1)(=O)=O.C(OCC)C>N1C=CC=CC=1>[CH:1]1([C:5]([O:7][C:28]2[CH:37]=[CH:36][C:35]3[C:30](=[CH:31][CH:32]=[C:33]([C:38](=[NH:39])[NH2:40])[CH:34]=3)[CH:29]=2)=[O:6])[CH2:4][CH2:3][CH2:2]1
Reactant: CS(=O)(=O)Oc1ccc2cc(C(=N)N)ccc2c1
Reactant: O=C(O)C1CCC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: c1ccncc1
Solvent: CCOCC
Product: N=C(N)c1ccc2cc(OC(=O)C3CCC3)ccc2c1
Reaction time: 0.5 h
Yield: 68.4 %

Procedure:
To a solution of 1.8 g of cyclobutanecarboxylic acid in 50 ml of anhydrous pyridine, while being cooled in ice and stirred, was added 4.4 g of DCC. After 30 minutes, 5.0 g of 6-amidino-2-naphthol methanesulfonate was added to the mixture and the mixture was further stirred for 24 hours at room temperature. The precipitate formed on addition of ethyl ether was collected by filtration, dissolved in dimethylformamide, and filtered to remove the insolubles. Ethyl ether was added to the filtrate and the precipitate which was formed was collected by filtration and recrystallized from a dimethylformamide-ethyl ether mixture to yield 3.3 g of a white powder of 6-amidino-2-naphthyl cyclobutanecarboxylate methanesulfonate.