Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([C@@H:10]2[C@@H:15]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[NH:14][C:13](=[O:23])[C@:12]([CH2:25][C:26]([O:28][CH3:29])=[O:27])([CH3:24])[CH2:11]2)[CH:7]=[CH:8][CH:9]=1.[N+:30](C1C=C([N+]([O-])=O)C=CC=1ON)([O-])=O>CN(C=O)C>[NH2:30][N:14]1[C@H:15]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)[C@@H:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([Cl:3])[CH:5]=2)[CH2:11][C@@:12]([CH2:25][C:26]([O:28][CH3:29])=[O:27])([CH3:24])[C:13]1=[O:23]
Reactant: NOc1ccc([N+](=O)[O-])cc1[N+](=O)[O-]
Reactant: COC(=O)C[C@@]1(C)C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)NC1=O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)C[C@@]1(C)C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)N(N)C1=O
Temperature: 23 °C
Reaction time: 0.25 h

Procedure:
A suspension of 60% sodium hydride in mineral oil (0.953 g, 23.82 mmol) was added to solution of methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetate (Example 429, step A, 4.84 g, 11.9 mmol) in DMF (25 mL). The resulting mixture was stirred for 15 min at 23° C. O-(2,4-dinitrophenyl)hydroxylamine (4.74 g, 23.82 mmol) was added at room temperature. The solution was stirred for 1 h at room temperature then quenched with MeOH (1 mL). Excess solvent was removed under reduced pressure and the residue was purified by chromatography on silica (eluent: 0 to 5% MeOH in DCM; stepwise gradient) to give the title compound. Mass Spectrum (ESI) m/z=421 (M+1), 443 (M+23).
Reaction SMILES: Cl.[C:2]([C:4]1[CH:5]=[C:6]([N:10]([CH:22]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=2)=[O:12])[CH:7]=[CH:8][CH:9]=1)#[N:3].C(=O)([O-])[O-].[NH4+:33].[NH4+:34]>C(O)C>[C:2]([C:4]1[CH:5]=[C:6]([N:10]([CH:22]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([C:20](=[NH:34])[NH2:21])=[CH:18][CH:19]=2)=[O:12])[CH:7]=[CH:8][CH:9]=1)(=[NH:33])[NH2:3]
Reactant: [NH4+]
Reactant: N#Cc1ccc(NC(=O)N(c2cccc(C#N)c2)C2CCCCCC2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CCO
Product: N=C(N)c1ccc(NC(=O)N(c2cccc(C(=N)N)c2)C2CCCCCC2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Dry hydrogen chloride gas was bubbled through an ice cooled solution of N-(3-cyanophenyl)-N'-(4-cyanophenyl)cycloheptylurea (0.065 g, 0.21 mmol) in anhydrous ethanol (5 ml) under a nitrogen atmosphere for 15 min. The reaction was stoppered and allowed to warm to ambient temperature and stir overnight. The reaction was concentrated in vacuo to give a white amorphous solid. This was dissolved in anhydrous ethanol (5 ml) and ammonium carbonate (0.118 g, 1.23 mmol) was added. The reaction was stirred under a nitrogen atmosphere at ambient temperature overnight. The reaction mixture was concentrated in vacuo to give a white solid. The product was purified by HPLC on a Vydec® C-18 column eluting with solvent mixture A (acetonitrile:water:TFA 80:20:0.3) and solvent mixture B (water:TFA 99.7:0.3) using a gradient starting with A:B at 3:97 and changing to A:B at 70:30 over 20 minutes. The major fraction was concentrated to give N-(3-amidinophenyl)-N'-(4-amidinophenyl)cycloheptylurea as a white solid (mp204-206° C.); LRMS (M+H)+ m/z 351, (M+2H)+2 m/z 176.2; HRMS calc. 351.1933, found 351.1936; 1H NMR (DMSO-d6): 9.4(bs, 2H), 9.2(broad s, 2H), 9.18 (broad s, 2H), 7.95 (broad s, 2H), 7.8-7.5(m, 6H), 7.47 (d, 2H), 3.9(bd, 4H), 1.83(m, 4H).
Reaction SMILES: [F:1][S:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[S:11](Cl)(=[O:13])=[O:12])(=[O:4])=[O:3].[NH:15]1[CH2:18][CH2:17][CH2:16]1.C(N(CC)CC)C>C(#N)C>[N:15]1([S:11]([C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[S:2]([F:1])(=[O:4])=[O:3])(=[O:13])=[O:12])[CH2:18][CH2:17][CH2:16]1
Reactant: O=S(=O)(F)c1ccccc1S(=O)(=O)Cl
Reactant: C1CNC1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: O=S(=O)(F)c1ccccc1S(=O)(=O)N1CCC1
Reaction time: 8 h
Yield: 100.2 %

Procedure:
In a flask was placed 9.24 g of 2-fluorosulfonylbenzenesulfonyl chloride and 200 ml of dry acetonitrile. The resultant solution was cooled to 0° C. An addition funnel was charged with 2 g of azetidine, 4.95 ml of triethylamine and 50 ml of acetonitrile. This solution was added dropwise to the first solution. After stirring overnight the solvent was evaporated under reduced pressure. The residue was partitioned between dichloromethane and 1N hydrochloric acid. The organic layer was separated, dried and concentrated to give 9.80 g of a solid, m.p. 93° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1/[CH:11]=[CH:12]/[C:13]1[S:14][CH:15]=[C:16]([CH:18]([CH3:20])[CH3:19])[N:17]=1.O.O.[Sn](Cl)Cl.[OH-].[Na+]>C(O)C>[NH2:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[C:3](/[CH:11]=[CH:12]/[C:13]2[S:14][CH:15]=[C:16]([CH:18]([CH3:19])[CH3:20])[N:17]=2)[CH:4]=1
Reactant: CC(C)c1csc(/C=C/c2cc([N+](=O)[O-])ccc2Cl)n1
Agent: Cl[Sn]Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CC(C)c1csc(/C=C/c2cc(N)ccc2Cl)n1
Temperature: 0 °C

Procedure:
A solution composed of 3.0 g of (E)-2-[2-(2-chloro-5-nitrophenyl)ethenyl]-4-(1-methylethyl)thiazole, 8.0 g of tin(II) chloride dihydrate and 100 ml of ethyl alcohol was heated to reflux for 1 hr. The reaction mixture was then condensed to half of its original volume, diluted with ice water, basified with 3N sodium hydroxide and extracted with methylene chloride. The combined extracts were washed with water and brine, dried (MgSO4) and condensed in vacuo to yield (E)-2-[2-(5-amino-2-chlorophenyl)ethenyl]-4-(1-methylethyl)thiazole; m.p. 82°-85° C. from hexane.
Reaction SMILES: [CH2:1]([O:8][C:9]([CH2:11][C:12]1([CH2:18][C:19](O)=[O:20])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO>O1CCCC1>[CH2:1]([O:8][C:9](=[O:10])[CH2:11][C:12]1([CH2:18][CH2:19][OH:20])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)CC1(CC(=O)OCc2ccccc2)CCCCC1
Solvent: CO
Solvent: C1CCOC1
Product: O=C(CC1(CCO)CCCCC1)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 79.6 %

Procedure:
A solution of (1-benzyloxycarbonylmethyl-cyclohexyl)-acetic acid (3.0 g, 10 mmol) in tetrahydrofuran (20 mL) was cooled to 0° C. and 1 M borane-THF complex in tetrahydrofuran (21 mL, 20 mmol) was added dropwise over 5 min. The reaction mixture was allowed to warm to room temperature, stirred for 1 h at room temperature. and cooled to 0° C. Methanol was added slowly to quench the reaction. The reaction mixture was warmed to room temperature, stirred for 30 min, and concentrated to dryness to provide the title compound (2.2 g).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][CH:9]=[CH:10][C:3]=12.[C:11]([CH2:13][C:14]1([N:25]2[CH:29]=[C:28](B3OC(C)(C)C(C)(C)O3)[CH:27]=[N:26]2)[CH2:17][N:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:15]1)#[N:12].C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.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:11]([CH2:13][C:14]1([N:25]2[CH:29]=[C:28]([C:2]3[CH:7]=[CH:6][N:5]=[C:4]4[NH:8][CH:9]=[CH:10][C:3]=34)[CH:27]=[N:26]2)[CH2:17][N:16]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:15]1)#[N:12]
Reactant: Brc1ccnc2[nH]ccc12
Reactant: CC(C)(C)OC(=O)N1CC(CC#N)(n2cc(B3OC(C)(C)C(C)(C)O3)cn2)C1
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: C1COCCO1
Solvent: O
Product: CC(C)(C)OC(=O)N1CC(CC#N)(n2cc(-c3ccnc4[nH]ccc34)cn2)C1
Temperature: 100 °C
Reaction time: 8 h
Yield: 25.7 %

Procedure:
A mixture of 4-bromo-1H-pyrrolo[2,3-b]pyridine (1.1 g, 5.7 mmol), tert-butyl 3-(cyanomethyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]azetidine-1-carboxylate (2.00 g, 5.15 mmol) (Example 40, Step 1), tetrakis(triphenylphosphine)palladium(0) (0.30 g, 0.26 mmol) and sodium carbonate (1.64 g, 15.4 mmol) in 1,4-dioxane (100 mL) and water (50 mL) under N2 (g) was stirred at 100° C. overnight. The reaction mixture was extracted with ethyl acetate (3×20 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure until 5 mL of solvent was left. The resulting precipitate (0.90 g) was collected by filtration and washed with ether. The filtrate was further concentrated under reduced pressure to a volume of about 3 mL. The precipitate formed was filtered, and washed with ether to afford additional product (0.50 g). The filtrate was concentrated under reduced pressure again. The residue was purified by flash chromatography on a silica gel column with methanol in dichloromethane (0-5%) to afford additional desired product (0.55 g). Total amount of product was 1.95 g (yield: 92.3%). LCMS (M+H)+: m/z=379.1.
Reaction SMILES: O.[OH-].[Li+].C[O:5][C:6](=[O:37])[CH2:7][C:8]1[C:17]([CH3:18])=[C:16]([C:19]2[CH:24]=[CH:23][C:22]([S:25]([C:28]3[CH:33]=[C:32]([F:34])[CH:31]=[C:30]([F:35])[CH:29]=3)(=[O:27])=[O:26])=[CH:21][CH:20]=2)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([Cl:36])[CH:14]=2)[CH:9]=1>C1COCC1.O>[Cl:36][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH2:7][C:6]([OH:37])=[O:5])[C:17]([CH3:18])=[C:16]2[C:19]1[CH:20]=[CH:21][C:22]([S:25]([C:28]2[CH:29]=[C:30]([F:35])[CH:31]=[C:32]([F:34])[CH:33]=2)(=[O:27])=[O:26])=[CH:23][CH:24]=1
Reactant: COC(=O)Cc1cc2ccc(Cl)cc2c(-c2ccc(S(=O)(=O)c3cc(F)cc(F)c3)cc2)c1C
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Cc1c(CC(=O)O)cc2ccc(Cl)cc2c1-c1ccc(S(=O)(=O)c2cc(F)cc(F)c2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 77.5 %

Procedure:
Lithium hydroxide monohydrate (0.019 g, 0.46 mmol) was added to a stirred solution of {6-chloro-4-[4-(3,5-difluoro-benzenesulfonyl)-phenyl]-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (0.057 g, 0.114 mmol) in a 3:1 THF—H2O mixture (4 mL). The reaction mixture was stirred for 16 hours at room temperature. The THF was distilled off under reduced pressure, and the crude residue was diluted with water, acidified [pH˜2] via the drop-wise addition of an aqueous solution of hydrochloric acid (6.0 N). The mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. Trituration with hexanes afforded {6-chloro-4-[4-(3,5-difluoro-benzenesulfonyl)-phenyl]-3-methyl-naphthalen-2-yl}-acetic acid (0.043 g, 77%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.51 (br. s, 1 H) 8.23 (d, J=7.82 Hz, 2 H) 7.97 (d, J=8.80 Hz, 1 H) 7.86-7.93 (m, 3 H) 7.70-7.78 (m, 1 H) 7.56 (d, J=8.80 Hz, 2 H) 7.48 (d, J=8.80 Hz, 1 H) 6.96 (s, 1 H) 3.85 (s, 2 H) 2.03 (s, 3 H) MS calcd. for C25H16ClF2O4S [(M−H)−] 485, obsd. 485.2.
Reaction SMILES: [Cl:1][C:2]1[C:3]([N:9]2[C:13]([C:14](O)=[O:15])=[CH:12][C:11]([CH3:17])=[N:10]2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[Cl:18]CCl.C(Cl)(=O)C(Cl)=O>CN(C)C=O>[Cl:1][C:2]1[C:3]([N:9]2[C:13]([C:14]([Cl:18])=[O:15])=[CH:12][C:11]([CH3:17])=[N:10]2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: Cc1cc(C(=O)O)n(-c2ncc(Cl)cc2Cl)n1
Reactant: ClCCl
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Product: Cc1cc(C(=O)Cl)n(-c2ncc(Cl)cc2Cl)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 100 %

Procedure:
To a 100 mL flask, 1-(3,5-dichloropyridin-2-yl)-3-methyl-1H-pyrazole-5-carboxylic acid (0.37 g, 1.38 mmol), dichloromethane (10 mL) and oxalyl dichloride (0.35 g, 2.20 mmol) were added. After a drop of N,N-dimethyl formamide was added, a large number of gas was released. After being stirred for overnight at room temperature, the reaction mixture was concentrated under reduced pressure. Then 10 mL toluene was added, and the mixture was concentrated again under reduced pressure to give the product (0.40 g) as yellow oil in 100% yield.
Reaction SMILES: [Br:1][C:2]1[CH:18]=[CH:17][C:5]([C:6]([CH:8]2[CH2:13][CH2:12][N:11]([C:14](=[O:16])[CH3:15])[CH2:10][CH2:9]2)=O)=[C:4](F)[CH:3]=1.C[NH:21][NH2:22]>C(O)CCC>[C:14]([N:11]1[CH2:12][CH2:13][CH:8]([C:6]2[C:5]3[C:4](=[CH:3][C:2]([Br:1])=[CH:18][CH:17]=3)[NH:22][N:21]=2)[CH2:9][CH2:10]1)(=[O:16])[CH3:15]
Reactant: CNN
Reactant: CC(=O)N1CCC(C(=O)c2ccc(Br)cc2F)CC1
Solvent: CCCCO
Product: CC(=O)N1CCC(c2n[nH]c3cc(Br)ccc23)CC1

Procedure:
A solution of 3.3 g of 4-(4-bromo-2-fluorobenzoyl)-1-acetylpiperidine, 1.1 g (0.013 mole) of methylhydrazine and 30 ml of n-butanol was heated under reflux for 16 hrs. The reaction mixture was concentrated in vacuo and the residue was diluted with water. The aqueous suspension was made basic with ammonium hydroxide solution and extracted with dichloromethane. The extract was washed with water, dried over anhydrous potassium carbonate and the solvent was concentrated to give 3-(1-acetyl-4-piperidinyl)-6-bromo-1H-indazole, as an oil.
Reaction SMILES: Cl.[OH:2][CH:3]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH3:16])[C:4](=[NH:8])[O:5]CC.C(N(CC)CC)C.[C:24](Cl)(Cl)=[O:25]>O1CCCC1>[CH3:16][O:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[CH:3]1[O:2][C:24](=[O:25])[NH:5][C:4]1=[O:8]
Reactant: CCOC(=N)C(O)c1ccccc1OC
Reactant: O=C(Cl)Cl
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COc1ccccc1C1OC(=O)NC1=O
Reaction time: 1 h
Yield: 42 %

Procedure:
Ethyl 1-hydroxy-1-(2-methoxyphenyl)methanecarboximidate hydrochloride (18 g., 0.073 mole) was suspended in 500 ml. of tetrahydrofuran, cooled to 0°-5° C., and triethylamine (23.6 g., 0.234 mole) was added. The stirred reaction mixture was perfused with phosgene for 30 minutes. Stirring at 0°-5° C. was continued for 1 hour. The reaction mixture was slowly poured over 1 l. of crushed ice and product extracted into three portions of chloroform. The combined chloroform extracts were washed with brine, dried over anhydrous magnesium sulfate, filtered and evaporated to solids. The residue was recrystallized from toluene to yield 5-(2-methoxyphenyl)oxazolidine-2,4-dione (6.4 g., 42%; m.p. 175°-177° C.; m/e 207). A second drop (3.7 g., 24%, m.p. 175°-177° C.) was obtained from the toluene mother liquor.
Reaction SMILES: Cl[C:2]1[C:3]2[N:4]([C:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[C:13]([CH3:15])[N:14]=2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.CC1(C)C(C)(C)OB([C:29]2[O:33][C:32]([Si](C(C)C)(C(C)C)C(C)C)=[N:31][CH:30]=2)O1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.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>[CH3:15][C:13]1[N:14]=[C:3]2[C:2]([C:29]3[O:33][CH:32]=[N:31][CH:30]=3)=[CH:7][C:6]([C:8]([F:11])([F:10])[F:9])=[CH:5][N:4]2[C:12]=1[C:16]([O:18][CH2:19][CH3:20])=[O:17]
Reactant: CCOC(=O)c1c(C)nc2c(Cl)cc(C(F)(F)F)cn12
Reactant: CC(C)[Si](c1ncc(B2OC(C)(C)C(C)(C)O2)o1)(C(C)C)C(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: [K+]
Solvent: COCCOC
Solvent: O
Product: CCOC(=O)c1c(C)nc2c(-c3cnco3)cc(C(F)(F)F)cn12
Temperature: 120 °C
Reaction time: 0.5 h
Yield: 18.6 %

Procedure:
A mixture of ethyl 8-chloro-2-methyl-6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxylate (380 mg), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(triisopropylsilyl)oxazole (479 mg), tetrakis(triphenylphosphine)palladium(0) (143 mg) and potassium carbonate (343 mg) in DME/water (8/2 mL) was stirred with microwave irradiation at 120° C. for 30 min. The reaction mixture was diluted with water, and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was dissolved in THF (12 mL), and 1N hydrochloric acid (4 mL) was added thereto. The reaction mixture was stirred at room temperature for 2 hr, saturated aqueous sodium bicarbonate solution was added thereto, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and the obtained solid was recrystallized from ethyl acetate/hexane to give the title compound (78 mg).
Reaction SMILES: [Cl:1][CH:2]([Cl:15])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9]([N:12]=[C:13]=[O:14])(=[O:11])=[O:10].[NH2:16][C:17]1[N:22]=[C:21]([O:23][CH3:24])[N:20]=[C:19]([CH3:25])[N:18]=1>C(#N)C>[Cl:15][CH:2]([Cl:1])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[S:9]([NH:12][C:13]([NH:16][C:17]1[N:22]=[C:21]([O:23][CH3:24])[N:20]=[C:19]([CH3:25])[N:18]=1)=[O:14])(=[O:11])=[O:10]
Reactant: COc1nc(C)nc(N)n1
Reactant: O=C=NS(=O)(=O)c1ccccc1C(Cl)Cl
Solvent: CC#N
Product: COc1nc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2C(Cl)Cl)n1
Reaction time: 18 h

Procedure:
2-(Dichloromethyl)benzenesulfonyl isocyanate prepared from 10 mmol of sulfonamide as described in the synthesis of Example 1, was treated with acetonitrile (15 ml) and 2-amino-4-methoxy-6-methyl-1,3,5-triazine (1.40 g). The mixture was stirred for 18 hrs. and filtered. The filtrate was evaporated and recrystallized from acetone to give 0.78 g of white solid, mp. 168°-169° (dec). 1H nmr δDMSO-d6TMS 8.37-7.50 (m, featuring singlet at 8.07), 7.00-6.17 (brds), 4.00 (s), 2.48 (s). IR (nujol) featured bands at 1720 and 1590 cm-1. Mass spectrum featured 264.9367 (calc'd for C8H5Cl2NO3S 264.9367) and 140.0687 (calc'd for C5H8N4O 140.0697).
Reaction SMILES: [C:1]([O-:8])(=[O:7])[CH2:2][CH2:3][C:4]([O-:6])=[O:5].[Na+].[Na+].[C:11]([N:15]=[N:16][C:17](Cl)([CH2:19][CH:20]([CH3:22])[CH3:21])[CH3:18])([CH3:14])([CH3:13])[CH3:12]>CN(C)C=O>[C:1]([O:8][C:17]([N:16]=[N:15][C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:18])[CH2:19][CH:20]([CH3:21])[CH3:22])(=[O:7])[CH2:2][CH2:3][C:4]([O:6][C:17]([N:16]=[N:15][C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:18])[CH2:19][CH:20]([CH3:22])[CH3:21])=[O:5]
Reactant: O=C([O-])CCC(=O)[O-]
Reactant: CC(C)CC(C)(Cl)N=NC(C)(C)C
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)CC(C)(N=NC(C)(C)C)OC(=O)CCC(=O)OC(C)(CC(C)C)N=NC(C)(C)C
Temperature: 25 °C
Reaction time: 3 h
Yield: 59.7 %

Procedure:
To a slurry of 5.97 grams (.0221 moles) of sodium succinate in 75 mls. of dimethylformamide in a 200 beaker, warmed to 35°C in a water bath, was added 9.0 grams (.0442 moles) of 2-t-butylazo-2-chloro-4-methylpentane dropwise. After the addition was complete, the reaction was stirred for 3 hours at room temperature, poured into 200 ml. of cold water and extracted with pentane. The pentane solution was washed with water, dried over anhydrous Na2SO4, filtered, stirred over alumina, filtered and the pentane evaporated to leave 6.0 grams (60% yield) of a light yellow liquid. The crude product was purified by column chromatography using pentane as eluent. The infrared spectrum of the purified product was in agreement with the structure of the desired product.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Cl[C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[N:9]=1.C(=O)([O-])O.[Na+]>C(O)CO>[N:1]1([C:8]2[CH:17]=[CH:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1
Reactant: C1CNCCN1
Reactant: Clc1ccc2ccccc2n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: OCCO
Product: c1ccc2nc(N3CCNCC3)ccc2c1
Temperature: 140 °C
Reaction time: 2 h
Yield: 102.2 %

Procedure:
To a solution formed by dissolving 4.31 g of anhydrous piperazine in 30 ml of ethylene glycol, 818 mg of 2-chloroquinoline was added, and stirred at 140° C. for 2 hours. After cooling the reaction mixture, saturated aqueous sodium hydrogencarbonate solution was added, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified on silica gel column chromatography (chloroform:methanol=2:1) to provide 1.09 g (100%) of 2-piperazin-1-ylquinoline.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:15])[CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][C:8]=1[F:14])[CH3:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:23][C:24]1[S:28][C:27]([CH2:29][O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:33])[CH3:32])=[C:26]([O:38][CH3:39])[CH:25]=1>C(#N)C>[Si:31]([O:30][CH2:29][C:27]1[S:28][C:24]([CH2:23][O:13][C:10]2[CH:11]=[CH:12][C:7]([CH2:6][CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:15])=[C:8]([F:14])[CH:9]=2)=[CH:25][C:26]=1[O:38][CH3:39])([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:32])[CH3:33]
Reactant: CCOC(=O)CCc1ccc(O)cc1F
Reactant: COc1cc(CBr)sc1CO[Si](C)(C)C(C)(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)CCc1ccc(OCc2cc(OC)c(CO[Si](C)(C)C(C)(C)C)s2)cc1F
Yield: 21.6 %

Procedure:
To a solution of 3-(2-fluoro-4-hydroxy-phenyl)-propionic acid ethyl ester (1.03 g, 4.8 mmol) in acetonitrile (15 mL) is added potassium carbonate (2.31 g, 16.8 mmol) and (5-bromomethyl-3-methoxy-thiophen-2-ylmethoxy)-tert-butyl-dimethyl-silane (1.7 g, 4.8 mmol) at room temperature and the reaction mixture is refluxed for 3 hours. The reaction mixture is concentrated, diluted with water, and extracted with EtOAc (2×30 mL). The combined extracts are washed with water (15 mL) and saturated brine (15 mL), dried over Na2SO4, filtered, and concentrated. The crude material is purified by silica gel chromatography eluting with hexane:ethyl acetate (9.6:0.4) to give the title compound (0.5 g, 21%). 1H NMR (400 MHz, DMSO d6) δ 7.51 (s, 1H), 7.26-7.2 (t, J=8.4 Hz, 1H), 6.92-6.89 (d, J=12 Hz, 1H), 6.83-6.81 (d, J=7.6 Hz, 2H), 4.92 (s, 2H), 4.82 (s, 2H), 4.10-4.05 (q, J=6.4 Hz, 2H), 3.82 (s, 3H), 2.86-2.82 (t, J=16 Hz, 2H), 2.61-2.55 (m, 2H), 1.21-1.17 (t, J=6.8 Hz, 3H), 0.89 (s, 9H), 0.13 (s, 6H).
Reaction SMILES: [NH2:1][C:2]1[N:6]=[CH:5][NH:4][N:3]=1.[OH:7][C:8]([CH3:20])([CH3:19])[CH2:9][O:10][C:11]1([CH3:18])[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(O)(=O)C.C(=O)([O-])O.[Na+]>[CH3:20][C:8]([OH:7])([CH3:19])[CH2:9][O:10][C:11]1([CH3:18])[CH2:16][CH2:15][CH:14]([NH:1][C:2]2[N:6]=[CH:5][NH:4][N:3]=2)[CH2:13][CH2:12]1
Reactant: CC(C)(O)COC1(C)CCC(=O)CC1
Reactant: Nc1nc[nH]n1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Product: CC(C)(O)COC1(C)CCC(Nc2nc[nH]n2)CC1
Temperature: 25 °C
Reaction time: 15 h
Yield: 57.6 %

Procedure:
To a solution of 3-amino-1H-1,2,4-triazole (441 mg) and 4-(2-hydroxy-2-methylpropoxy)-4-methylcyclohexanone (1.05 g) in acetic acid (10 mL) was added sodium triacetoxyborohydride (1.67 g), and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate-isopropyl alcohol (3:1). The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography [eluent: methanol/ethyl acetate=0/100→10/90 (volume ratio)] to give colorless amorphous 2-methyl-1-{[1-methyl-4-(1H-1,2,4-triazol-3-ylamino)cyclohexyl]oxy}propan-2-ol (810 mg, 54%) as a diastereomixture.
Reaction SMILES: C([O:4][C@@H:5]1[C@H:9]([O:10]C(=O)C)[C@@H:8]([CH2:14][O:15]C(=O)C)[O:7][C@H:6]1[N:19]1[C:28]2[N:27]=[C:26]([I:29])[N:25]=[C:23]([NH2:24])[C:22]=2[N:21]=[C:20]1Br)(=O)C.[CH3:31][NH2:32]>>[I:29][C:26]1[N:25]=[C:23]([NH2:24])[C:22]2[N:21]=[C:20]([NH:32][CH3:31])[N:19]([C:28]=2[N:27]=1)[C@@H:6]1[O:7][C@H:8]([CH2:14][OH:15])[C@@H:9]([OH:10])[C@H:5]1[OH:4]
Reactant: CC(=O)OC[C@H]1O[C@@H](n2c(Br)nc3c(N)nc(I)nc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: CN
Product: CNc1nc2c(N)nc(I)nc2n1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O

Procedure:
The reaction was performed with 2′,3′,5′-tri-O-acetyl-2-iodo-8-bromoadenosine (6, 100 mg, 0.17 mmol) and methylamine (16 ml, 40% w/v in water). Yield 54.6 mg (0.13 mmol, 77%), mp 162–164÷C; 1H NMR (DMSO-d6) δ 7.02 (d, 1H, J=5.15 Hz, NH), 6.93 (s, 2H, NH2), 5.77 (d, 1H, J=7.56 Hz, H-1′), 5.66 (t, 1H, J=4.81 Hz, OH-2′), 5.31 (d, 1H, J=6.52 Hz, OH-5′), 5.18 (d, 1H, J=4.46 Hz, OH-3′), 4.56 (q, 1H, J=5.15 Hz, H-2′), 4.09–4.04 (m, 1H, H-3′), 3.98–3.91 (m, 1H, H-4′), 3.68–3.57 (m, 2H, H-5′), 2.86 (d, 3H, J=4.46 Hz, CH3); MS m/z 423 (M+H)+; Anal. (C11H15IN6O4) C, H, N.