Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[CH3:14][N:15]=[C:16]=[S:17]>ClCCl>[O:11]1[CH2:12][CH2:13][N:8]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[NH:1][C:16]([NH:15][CH3:14])=[S:17])[CH2:9][CH2:10]1
Reactant: CN=C=S
Reactant: Nc1ccccc1N1CCOCC1
Solvent: ClCCl
Product: CNC(=S)Nc1ccccc1N1CCOCC1
Temperature: 25 °C
Reaction time: 36 h

Procedure:
A solution of 4-(2-aminophenyl)morpholine (5.3 g) in dichloromethane (25 ml) was treated with methyl isothiocyanate (3.2 g) and the mixture stirred at room temperature for 36 hours to yield 1-(2-morpholinophenyl)-3-methylthiourea (m.p. 115°-116° C.) which was recrystallised from a 4:1 mixture of ethyl acetate and hexane.
Reaction SMILES: [CH3:1][C:2]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:3]=1[C:4](=[O:16])[CH2:5][CH:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:8](=O)[O:7]1.S(Cl)([Cl:24])=O>C1C=CC=CC=1>[CH3:1][C:2]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:3]=1[C:4]([CH:5]=[CH:6][C:15]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[C:8]([Cl:24])=[O:7])=[O:16]
Reactant: O=S(Cl)Cl
Reactant: Cc1ccc(C)c(C(=O)CC2OC(=O)c3ccccc32)c1
Solvent: c1ccccc1
Product: Cc1ccc(C)c(C(=O)C=Cc2ccccc2C(=O)Cl)c1

Procedure:
A 1 liter flask was charged with 32.2 grams (115 mmol) of 3-(2',5'-dimethylphenacyl)phthalide, 200 ml of benzene and 50 ml of thionyl chloride. After heating at reflux on a steambath for 30 minutes, the solution was concentrated. The residue was triturated with ligroin to give 32.5 grams of o-(2',5'-dimethylbenzoylvinyl)benzoyl chloride, m.p. 96°-98° C. Analysis shows 72.29% carbon, 5.07% hydrogen and 11.80% chlorine as against calculated values of 72.36%, 5.06% and 11.87% for C18H15ClO2.
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][C@H:3]1[F:15].C(=O)(O)[O-].[Na+].Cl[C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23]>C(Cl)Cl.O>[CH2:25]([O:24][C:22]([NH:1][C@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:14])[CH3:13])=[O:9])[CH2:4][C@H:3]1[F:15])=[O:23])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CC(C)(C)OC(=O)N1CC[C@H](N)[C@H](F)C1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: CC(C)(C)OC(=O)N1CC[C@H](NC(=O)OCc2ccccc2)[C@H](F)C1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 92.9 %

Procedure:
(3R,4S)-tert-butyl 4-amino-3-fluoropiperidine-1-carboxylate (300 mg, 1.374 mmol) was taken up in DCM (8 mL) and a solution of sodium bicarbonate (346 mg, 4.12 mmol) in water (1 mL) was added. The reaction mixture was cooled to 0° C. and benzyl chloroformate (0.235 mL, 1.649 mmol) was added dropwise. The reaction was stirred at 0° C. for 30 min, then brought to rt and stirred overnight. The reaction mixture was diluted with DCM and water, and the organic layer was collected. The aqueous layer was reextracted with DCM and the organic layers were combined, dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography, eluting with 0-30% EtOAc/Hex. The fractions were combined and concentrated to give (3R,4S)-tert-butyl 4-(((benzyloxy)carbonyl)amino)-3-fluoropiperidine-1-carboxylate (450 mg) as a colorless glass.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12](Br)=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2OC2C=CC=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:55][C:56]1[S:57][CH:58]=[CH:59][N:60]=1.C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([NH:55][C:56]2[S:57][CH:58]=[CH:59][N:60]=2)=[N:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Brc1ccc(OCc2ccccc2)cn1
Reactant: Nc1nccs1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2Oc2ccccc2P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: c1ccc(COc2ccc(Nc3nccs3)nc2)cc1
Yield: 34 %

Procedure:
5-Benzyloxy-2-bromo-pyridine (0.25 mmol), sodium-tert.-butylate (1.4 eq.), tris-(dibenzylideneaceton)-dipalladium (0.1 eq.), bis(2-diphenylphosphinophenyl)-ether (0.4 eq.) and 2-amino-thiazole (1.5 eq.) are filled under nitrogen in a microwave reaction vessel. Degassed toluene (45 eq.) is added. The reaction suspension is heated for 60 min to 150° C. and 60 minutes to 180° C. Ethyl acetate is added to the reaction suspension and filtrated over celite. The solvent of the filtrate is removed in vacuo. (5-Benzyloxy-pyridine-2-yl)-thiazole-2-yl-amine (“A30”) is obtained after reversed phase column chromatography (water/acetonitrile+0.1% TFA) as orange oil in a yield of 34%. HPLC (method C): 1.69 min; LC-MS (method A): 1.44 min, 285.15 (MH+); 1H-NMR (DMSO-d6, 500 MHz): δ [ppm] 11.108 (s, 1H), 8.072 (d, 1H, J=2.9 Hz), 7.500-7.447 (m, 3H), 7.412-7.383 (m, 2H), 7.349-7.320 (m, 2H), 7.064 (d, 1H, J=9 Hz), 6.926 (d, 1H, J=3.5 Hz), 5.139 (s, 2H).
Reaction SMILES: C(OC([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][C:17]2([C:22]([O:24][CH3:25])=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:12][CH2:11]1)=O)(C)(C)C>C(Cl)Cl.FC(F)(F)C(O)=O>[NH2:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][C:17]2([C:22]([O:24][CH3:25])=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:12][CH2:11]1
Reactant: COC(=O)C1(CN2CCC(CNC(=O)OC(C)(C)C)CC2)CCCC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)C1(CN2CCC(CN)CC2)CCCC1
Yield: 99.9 %

Procedure:
A solution of methyl 1-[(4-{[(tert-butoxycarbonyl)amino]methyl}piperidine-1-yl)methyl]cyclopentanecarboxylate (1.16 g, 3.27 mmol, Step 2) in CH2Cl2 (25 mL) and trifluoroacetic acid (5 mL) was stirred at room temperature for 1.5 h. The reaction mixture was then concentrated and basified with sat. NaHCO3 aq. (100 mL), extracted with CHCl3 (100 mL) for five times. The combined extract was dried and concentrated to give 0.831 g (100%) of title compound as yellow syrup.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:21]=[CH:20][C:6]([O:7][CH2:8][C:9]2[N:10]=[C:11]([C:15]3[O:16][CH:17]=[CH:18][CH:19]=3)[O:12][C:13]=2[CH3:14])=[C:5]([O:22][CH3:23])[CH:4]=1.[OH:24][C:25]1[C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:28][N:27]([CH2:35][C:36]2[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=2)[N:26]=1.CN(C)C=O.[H-].[Na+]>O>[O:16]1[CH:17]=[CH:18][CH:19]=[C:15]1[C:11]1[O:12][C:13]([CH3:14])=[C:9]([CH2:8][O:7][C:6]2[CH:20]=[CH:21][C:3]([CH2:2][O:24][C:25]3[C:29]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:28][N:27]([CH2:35][C:36]4[CH:37]=[N:38][CH:39]=[CH:40][CH:41]=4)[N:26]=3)=[CH:4][C:5]=2[O:22][CH3:23])[N:10]=1
Reactant: CCOC(=O)c1cn(Cc2cccnc2)nc1O
Reactant: COc1cc(CCl)ccc1OCc1nc(-c2ccco2)oc1C
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1cn(Cc2cccnc2)nc1OCc1ccc(OCc2nc(-c3ccco3)oc2C)c(OC)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 66.9 %

Procedure:
To a mixture of 4-{[4-(chloromethyl)-2-methoxyphenoxy]methyl}-2-(2-furyl)-5-methyl-1,3-oxazole (0.94 g), ethyl 3-hydroxy-1-(pyridin-3-ylmethyl)-1H-pyrazole-4-carboxylate (0.55 g) and N,N-dimethylformamide (20 mL) was added sodium hydride (60% in oil, 0.10 g) at room temperature. After stirring the reaction mixture at room temperature for 1 hr, the mixture was further stirred at 90° C. for 1 hr. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography to give ethyl 3-[(4-{[2-(2-furyl)-5-methyl-1,3-oxazol-4-yl]methoxy}-3-methoxybenzyl)oxy]-1-(pyridin-3-ylmethyl)-1H-pyrazole-4-carboxylate as colorless crystals (0.81 g, yield 68%) from a fraction eluted with ethyl acetate-methanol (20:1, v/v). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 131-132° C.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:12][CH3:13])[CH:8]=2)[CH:3]=1.[C:14]1([Mg]Br)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[CH3:13][O:12][C:7]1[CH:6]=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:3]=2)[CH:8]=1
Reactant: Br[Mg]c1ccccc1
Reactant: COc1ccc2cc(Br)ccc2c1
Product: COc1ccc2cc(-c3ccccc3)ccc2c1

Procedure:
The title compound was prepared by reacting 2-bromo-6-methoxynaphthalene (1.97 g, 8.31 mmol) with phenylmagnesium bromide according to the method used to prepare intermedite 10 to yield 1.59 g (82%) of a white solid: mp 122–126° C.; 1H NMR (CDCl3): δ 3.94 (3H, s), 7.16–7.18 (2H, m), 7.34–7.37 (1H, m), 7.46–7.49 (2H, m), 7.69–7.72 (2H, m), 7.78–7.82 (2H, m), 7.97 (1H, t); MS (El) m/z 234.2 (M)+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:23])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2Br)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].O.C(O[CH2:35][CH3:36])(=O)C>CN(C)C=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:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14](=[O:23])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:10]2[CH:9]=[N:8][CH:6]=[CH:35][CH:36]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)Cc2ccccc2Br)CC1
Reactant: CCOC(C)=O
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: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC(C(=O)Cc2ccccc2-c2cccnc2)CC1
Temperature: 100 °C
Reaction time: 2 h
Yield: 66 %

Procedure:
After dissolving 575 mg of 1-[1-(tert-butoxycarbonyl)piperidin-4-yl]-2-(2-bromophenyl)ethanone in 10 ml of N,N-dimethylformamide, there were added 489 mg of 2-(3-pyridyl)-1,3,2-dioxabornane, 173 mg of tetrakis(triphenylphosphine)palladium(0) and 1.47 g of anhydrous cesium carbonate, and the mixture was stirred at 100° C. for 2 hours under a nitrogen atmosphere. Water was added to the reaction mixture, and extraction was performed with ethyl acetate. The organic layer was washed with water and saturated brine in that order and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (379 mg, 66% yield).
Reaction SMILES: [CH3:1]I.[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:8][C:9]=1[OH:10]>C(Cl)(Cl)Cl.C(=O)([O-])[O-].[Ag+2]>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[N:8][C:9]=1[O:10][CH3:1]
Reactant: CI
Reactant: CCOC(=O)c1ccc(Cl)c(O)n1
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Solvent: ClC(Cl)Cl
Product: CCOC(=O)c1ccc(Cl)c(OC)n1
Temperature: 70 °C
Reaction time: 7 h
Yield: 80 %

Procedure:
Silver carbonate (142.4 g) and methyl iodide (25 mL) were added to a solution of ethyl 5-chloro-6-hydroxypyridine-2-carboxylate (26.0 g) in chloroform (500 mL), and the mixture was stirred at 70° C. for seven hours. The reaction solution was filtered through celite, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=30:1) and purified again by silica gel column chromatography (hexane:ethyl acetate=20:1) to give ethyl 5-chloro-6-methoxypyridine-2-carboxylate as a white solid (22.3 g, 80%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH2:7][OH:8])=[CH:5][CH:4]=1.[H-].[Na+].[Br:13][C:14]1[CH:23]=[C:22]2[C:17]([C:18](Cl)=[N:19][C:20](Cl)=[N:21]2)=[CH:16][CH:15]=1>C1(C)C=CC=CC=1>[Br:13][C:14]1[CH:23]=[C:22]2[C:17]([C:18]([O:8][CH2:7][C:6]3[CH:9]=[CH:10][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)=[N:19][C:20]([O:8][CH2:7][C:6]3[CH:9]=[CH:10][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)=[N:21]2)=[CH:16][CH:15]=1
Reactant: COc1ccc(CO)cc1
Reactant: Clc1nc(Cl)c2ccc(Br)cc2n1
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: COc1ccc(COc2nc(OCc3ccc(OC)cc3)c3ccc(Br)cc3n2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 83.4 %

Procedure:
199.0 ml (1.6 mol) of 4-methoxybenzyl alcohol in 0.5 l of toluene were added dropwise to a suspension of 95.8 g (2.4 mol) of sodium hydride [60% in paraffin oil] in 1.5 l of toluene between 15- and 20° C. The mixture was subsequently stirred at room temperature for a further 1 h. 193.6 g (0.67 mol) of 7-bromo-2,4-dichloroquinazoline were then added in portions, and the reaction mixture was stirred for 48 h. Conventional work-up gave 269.0 g of 7-bromo-2,4-bis(4-methoxybenzyloxy)quinazoline as oil [crude product; was reacted further directly].
Reaction SMILES: Br[C:2]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:3]=1[NH2:4].C(O[C:16]([S:18][K])=[S:17])C.O.Cl>CN(C)C=O>[F:10][C:9]([F:12])([F:11])[C:6]1[CH:7]=[CH:8][C:2]2[S:17][C:16]([SH:18])=[N:4][C:3]=2[CH:5]=1
Reactant: CCOC(=S)S[K]
Reactant: Nc1cc(C(F)(F)F)ccc1Br
Agent: Cl
Solvent: O
Solvent: CN(C)C=O
Product: FC(F)(F)c1ccc2sc(S)nc2c1
Temperature: 120 °C

Procedure:
Into a solution of 2-bromo-5-(trifluoromethyl)aniline (1.5 g, 6.25 mmol, 1.00 equiv) in N,N-dimethylformamide (10.0 mL) was added ethoxy(potassiosulfanyl)methanethione (2.2 g, 13.72 mmol, 2.20 equiv) under nitrogen. The resulting mixture was heated for 4 h at 120° C. in an oil bath. After cooled down, water (70.0 mL) and hydrogen chloride (15.0 mL, 1 mol/L) were added. The solid was collected by filtration, dissolved in ethyl acetate and dried over anhydrous sodium sulfate. Filtration and evaporation of the solvent afforded the title compound. as a gray white solid. MS m/z [M+H]+ (ESI): 236
Reaction SMILES: [C:1]1([C:11]([OH:13])=[O:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[CH2:14](O)[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].OS(O)(=O)=O>O>[CH2:14]([O:12][C:11]([C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)=[O:13])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: CCCCCCCCO
Reactant: O=C(O)c1cccc2ccccc12
Agent: O=S(=O)(O)O
Solvent: O
Product: CCCCCCCCOC(=O)c1cccc2ccccc12
Temperature: 120 °C
Yield: 80.9 %

Procedure:
One mol (172 g) of α-naphthoic acid, 1.5 mol (195 g) of octyl alcohol and 3 ml of conc. H2SO4 were charged into a four-necked flask, and the whole was heated to 120° C. under agitation for 5 hours in a nitrogen atmosphere. After the end of the reaction, the resulting reaction mixture was cooled, freed from the water, sulfuric acid, unreacted naphthoic acid and alcohol by the use of a separating funnel and then distilled under a reduced pressure to obtain 230 g of octyl-1-naphthoate having a boiling point of 200°-202° C./4 mmHg.
Reaction SMILES: Br[C:2]1[CH:14]=[CH:13][C:5]([C:6]([NH:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])=[C:4]([F:15])[CH:3]=1.[Cu][C:17]#[N:18].C(N)CN>CN(C=O)C>[C:9]([NH:8][C:6](=[O:7])[C:5]1[CH:13]=[CH:14][C:2]([C:17]#[N:18])=[CH:3][C:4]=1[F:15])([CH3:12])([CH3:11])[CH3:10]
Reactant: CC(C)(C)NC(=O)c1ccc(Br)cc1F
Reactant: N#C[Cu]
Solvent: NCCN
Solvent: CN(C)C=O
Product: CC(C)(C)NC(=O)c1ccc(C#N)cc1F
Temperature: 25 °C
Yield: 74.6 %

Procedure:
Combine 4-bromo-N-tert-butyl-2-fluoro-benzamide (1.0 g, 3.65 mmol) and copper(I) cyanide (0.7 g, 7.29 mmol) in anhydrous DMF (10 mL) and reflux for 17 h. Cool the reaction mixture to ambient temperature and treat with 50% (v/v) aqueous ethylenediamine (20 mL). Extract the reaction mixture with diethyl ether (3×10 mL), combine the organic extracts, wash with brine (2×10 mL) and dry the organic layer over Na2SO4. Evaporate the solvent and purify by chromatography on silica gel eluting with hexane/EtOAc (1:0, 9:1, 4:1, 7:3 and 3:2) to obtain the desired intermediate as a white solid (0.6 g, 77%). MS (ES+) m/z: 221 (M+H)+.
Reaction SMILES: [C:1]1([OH:21])[C:2]([C:11]2[CH:20]=[CH:19][C:18]3[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=3[CH:12]=2)=[CH:3][CH:4]=[C:5]2[C:10]=1[CH2:9][CH2:8][CH2:7][CH2:6]2.CS(O[CH:27]([CH3:29])[CH3:28])(=O)=O>[O-]S(C(F)(F)F)(=O)=O.[Sc+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O.C(Cl)(Cl)(Cl)Cl>[CH:27]([C:3]1[CH:4]=[C:5]2[C:10]([CH2:9][CH2:8][CH2:7][CH2:6]2)=[C:1]([OH:21])[C:2]=1[C:11]1[CH:20]=[CH:19][C:18]2[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=2[CH:12]=1)([CH3:29])[CH3:28]
Reactant: CC(C)OS(C)(=O)=O
Reactant: Oc1c(-c2ccc3c(c2)CCCC3)ccc2c1CCCC2
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [Sc+3]
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)c1cc2c(c(O)c1-c1ccc3c(c1)CCCC3)CCCC2
Reaction time: 18 h
Yield: 78 %

Procedure:
A mixture of 5,5′,6,6′,7,7′,8,8′-octahydro-2,2′-binaphthol (2 g, 6.8 mmol), isopropyl methanesulfonate (5.5 mmol), scandium triflate (0.34 g, 5 mol %), and carbon tetrachloride (10 ml) was brought to reflux under argon. After 18 hours, GC indicated 65% conversion to give 78% desired product. Additional isopropyl methanesulfonate (3.1 mmol) was added, and the reaction mixture was refluxed for another 8 hours. GC showed 86% conversion, and 76% selectivity to 3-isopropyl-5,5′,6,6′,7,7′,8,8′-octahydro-2,2′-binaphthol. The mixture was diluted with ether (20 ml) and 10% HCl (20 ml). The layers were separated, and the aqueous layer was extracted with ether (3×20 ml). The ether layers were combined, dried (MgSO4), and concentrated. The crude product was purified by column chromatography (SiO2, 2% ethyl acetate/hexanes) to yield 1.1 g white solid (48%). MP: 100–102° C.
Reaction SMILES: C(O[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[O:16][C:17]3[N:18]=[C:19]([C:24]#[C:25][C@@H:26]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH3:27])[N:20]=[CH:21][C:22]=3[N:23]=2)=[CH:11][CH:10]=1)C1C=CC=CC=1.[N+](C1C=CC(S([O:48][CH2:49][C@H:50]2[CH2:52][C:51]2([F:54])[F:53])(=O)=O)=CC=1)([O-])=O>>[F:54][C:51]1([F:53])[CH2:52][C@@H:50]1[CH2:49][O:48][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[O:16][C:17]3[N:18]=[C:19]([CH2:24][CH2:25][C@@H:26]([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH3:27])[N:20]=[CH:21][C:22]=3[N:23]=2)=[CH:13][CH:14]=1
Reactant: C[C@@H](C#Cc1ncc2nc(-c3ccc(OCc4ccccc4)cc3)oc2n1)NC(=O)OC(C)(C)C
Reactant: O=[N+]([O-])c1ccc(S(=O)(=O)OC[C@H]2CC2(F)F)cc1
Product: C[C@@H](CCc1ncc2nc(-c3ccc(OC[C@H]4CC4(F)F)cc3)oc2n1)NC(=O)OC(C)(C)C

Procedure:
Using tert-butyl ((2S)-4-(2-(4-(benzyloxy)phenyl) [1,3]oxazolo[5,4-d]pyrimidin-5-yl)but-3-yn-2-yl)carbamate and ((1R)-2,2-difluorocyclopropyl)methyl 4-nitrobenzenesulfonate, and in the same manner as in Step A of Example 4 and Example 5, the title compound was obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[CH:6][C:7]=1[Cl:8].[OH-].[Na+].[CH3:12][S:13]([C:16]1[CH:21]=[CH:20][C:19](Cl)=[C:18]([Cl:23])[CH:17]=1)(=[O:15])=[O:14].O>CS(C)=O>[Cl:23][C:18]1[CH:17]=[C:16]([S:13]([CH3:12])(=[O:15])=[O:14])[CH:21]=[CH:20][C:19]=1[O:9][C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=1
Reactant: CS(=O)(=O)c1ccc(Cl)c(Cl)c1
Reactant: Oc1ccc(Cl)c(Cl)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: O
Product: CS(=O)(=O)c1ccc(Oc2ccc(Cl)c(Cl)c2)c(Cl)c1
Temperature: 60 °C
Yield: 82.1 %

Procedure:
To a solution of 9.09 g (0.0558 mole) of 3,4-dichlorophenol dissolved in 150 ml of DMSO was added 2.23 g (0.0558 mole) of NaOH. The mixture was heated to 60° C. and 11.3 g (0.0502 mole) of 3,4-dichlorophenyl methyl sulfone was added and the mixture heated at 150° C. for 3.75 hrs. The mixture was cooled and poured into water. The crystalline product was collected by filtration, washed with water and dried, which gave 14.5 g (82.4% yield) of product. Recrystallization from ethanol afforded purified 4-(2-chloro-4-(methylsulfonyl)phenoxy)-1,2-dichlorobenzene, mp 102°-104° C.
Reaction SMILES: CN(C)C=O.[CH2:6](Cl)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C([C@@]1(O)[C@@H](CO)O[C@@](C(=O)C)([N:24]2[C:34]3[N:33]=[C:31]([NH2:32])[NH:30][C:28](=[O:29])[C:27]=3[N:26]=[CH:25]2)[C@]1(C(=O)C)O)(=O)C.Cl>CO>[CH2:6]([N:26]1[C:27]2[C:28](=[O:29])[NH:30][C:31]([NH2:32])=[N:33][C:34]=2[N:24]=[CH:25]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: ClCc1ccccc1
Reactant: CC(=O)[C@@]1(O)[C@@](O)(C(C)=O)[C@@H](CO)O[C@@]1(C(C)=O)n1cnc2c(=O)[nH]c(N)nc21
Agent: Cl
Solvent: CN(C)C=O
Solvent: CO
Product: Nc1nc2ncn(Cc3ccccc3)c2c(=O)[nH]1
Temperature: 25 °C
Reaction time: 22 h
Yield: 76.4 %

Procedure:
Four milliliters of N,N-dimethylformamide and 0.53 ml (2.49 equivalents) of benzyl chloride were added to 0.758 g (1.85 mmols) of triacetylguanosine, and the reaction was conducted at 60° C. for 22 hours. It was identified through liquid chromatography that 69% of the starting material remained. Accordingly, 1.60 ml (10 equivalents in total) of benzyl chloride were further added thereto, and the reaction was conducted at 60° C. for 23 hours and at 70° C. for 5 hours. The temperature was returned to room temperature, and 1.57 ml (10 equivalents) of conc. hydrochloric acid were added to the solution. The reaction was conducted for 2 hours, but the cleavage of the sugar moiety was not completed. Therefore, 1.58 ml (20 equivalents in total) of conc. hydrochloric acid were further added, and the mixture was stirred overnight at room temperature. Ten milliliters of methanol were added to the reaction solution in the slurry state. The mixture was stirred for 2 hours, and then filtered. The crystals were washed twice with 5 ml of methanol, dried at 50° C. under reduced pressure for 5 hours to give 0.444 g of 7-benzylguanine crystals in a yield of 76.4%.
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I:9][C:10]1[CH:18]=[CH:17][CH:16]=[CH:15][C:11]=1[C:12](Cl)=[O:13].C1C=CC=CC=1>O1CCCC1>[CH2:1]([NH:8][C:12](=[O:13])[C:11]1[CH:15]=[CH:16][CH:17]=[CH:18][C:10]=1[I:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccccc1I
Reactant: NCc1ccccc1
Solvent: c1ccccc1
Solvent: C1CCOC1
Product: O=C(NCc1ccccc1)c1ccccc1I

Procedure:
A solution of 15 ml of benzylamine in 20 ml of tetrahydrofuran was reacted with a solution of 8.0 g of o-iodobenzoyl chloride in 20 ml of tetrahydrofuran in accordance with the procedure of Example 3. There was obtained by recrystallization from benzene 9.1 g of N-benzyl-o-iodobenzamide, m.p. 122°-123°, Rf 0.78.
Reaction SMILES: C([O:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C@H:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:14][CH2:15][OH:16])=[CH:8][CH:7]=1)=[CH2:5])C.[Br:25]NC(=O)CCC(N)=O>O1CCCC1.O>[Br:25][CH2:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C@H:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:14][CH2:15][OH:16])=[CH:8][CH:7]=1)=[O:5]
Reactant: C=C(OCC)c1ccc(C[C@@H](CCO)NC(=O)OC(C)(C)C)cc1
Reactant: NC(=O)CCC(=O)NBr
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@H](CCO)Cc1ccc(C(=O)CBr)cc1
Temperature: 25 °C
Yield: 100 %

Procedure:
To a cooled (0° C.) solution of 1,1-dimethylethyl [(1S)-1-({4-[1-(ethyloxy)ethenyl]phenyl}methyl)-3-hydroxypropyl]carbamate (15 g, 44 mmol) in tetrahydrofuran (450 mL) and water (150 mL) was added N-bromosuccinamide. The resulting solution was allowed to warm to room temperature and maintained for 90 minutes. The reaction was then concentrated and diluted with ethyl acetate (1 L). The resulting solution was washed with water (1 L) and brine (500 mL), dried (MgSO4) and concentrated to give 19.5 g (˜100%) of 1,1-dimethylethyl ((1S)-1-{[4-(bromoacetyl)phenyl]methyl}-3-hydroxypropyl)carbamate as a slightly yellow solid. ESMS [M+H]+: 386.2.
Reaction SMILES: Cl[CH2:2][C:3]1[N:7]=[CH:6][N:5]([CH3:8])[N:4]=1.[CH3:9][NH2:10]>O1CCOCC1>[CH3:9][NH:10][CH2:2][C:3]1[N:7]=[CH:6][N:5]([CH3:8])[N:4]=1
Reactant: Cn1cnc(CCl)n1
Reactant: CN
Solvent: C1COCCO1
Product: CNCc1ncn(C)n1
Temperature: 80 °C
Yield: 80 %

Procedure:
A solution of 3-chloromethyl-1-methyl-1H-1,2,4-triazole (from Example 1, Step c; 600 mg, 4.6 mmol) in 40% aqueous methylamine and 1,4-dioxane (5 ml) was stirred and heated at 80° C. in a sealed tube for 16 hours. Upon cooling the whole mixture was evaporated (azeotroping with ethanol). The residue was purified by chromatography on silica gel, eluting with dichloromethane-methanol-aqueous ammonia (60:8:1→40:8:1) to give the title compound (440 mg, 80%) as a pale yellow oil. 1H NMR (250 MHz, d6-DMSO) δ 3.61 (2H, s), 3.81 (3H, s), 8.35 (1H, s); MS (ES+) m/e 127 [MH]+.