Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([N:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:27])[CH2:18][NH:19][C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=2)[CH2:13][CH2:12]1)[C:2]1[CH:10]=[CH:9][C:8]2[O:7][CH2:6][O:5][C:4]=2[CH:3]=1.C(O)(=O)C.C(O[C:35]1(O[Si](C)(C)C)[CH2:37][CH2:36]1)C.C([BH3-])#N.[Na+]>CO>[CH2:1]([N:11]1[CH2:16][CH2:15][N:14]([C:17](=[O:27])[CH2:18][N:19]([CH:35]2[CH2:37][CH2:36]2)[C:20]2[CH:21]=[CH:22][C:23]([OH:26])=[CH:24][CH:25]=2)[CH2:13][CH2:12]1)[C:2]1[CH:10]=[CH:9][C:8]2[O:7][CH2:6][O:5][C:4]=2[CH:3]=1
Reactant: CCOC1(O[Si](C)(C)C)CC1
Reactant: O=C(CNc1ccc(O)cc1)N1CCN(Cc2ccc3c(c2)OCO3)CC1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: O=C(CN(c1ccc(O)cc1)C1CC1)N1CCN(Cc2ccc3c(c2)OCO3)CC1
Temperature: 60 °C
Reaction time: 16 h

Procedure:
To a solution of 1-(4-piperonylpiperazin-1-yl)-2-(4-hydroxyphenylamino)ethanone (1.00 g, 2.7 mmol) in methanol (10 mL) were added acetic acid (1.55 mL, 27 mmol), molecular sieves 3A1/16 (1.00 g), [(1-ethoxycyclopropyl)oxy]trimethylsilane (0.653 mL, 3.2 mmol) and sodium cyanoborohydride (770 mg, 12 mmol). The resulting solution was stirred for 16 hours at 60° C. This reaction solution was filtered and concentrated, and to the residue were added ethyl acetate and water. The aqueous layer was adjusted to pH 10 using aqueous 6 N sodium hydroxide. This layer was stirred for some time, and once insoluble matter had dissolved, the ethyl acetate layer was removed, and washed with aqueous 2 N sodium hydroxide and a saturated sodium bicarbonate solution, then dried over anhydrous magnesium sulfate. The solvent was evaporated, to thereby yield 770 mg of the title compound.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@@H:11]3[O:26][C@H:25]([CH2:27][O:28][CH2:29][C:30]4[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=4[Cl:37])[C@@H:14]([O:15][CH2:16][C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=4[Cl:24])[C@@:12]3([CH:38]=C)[OH:13])[C:4]=2[N:5]=[CH:6][N:7]=1.C[N+]1([O-])CC[O:44]CC1.[BH4-].[Na+]>O1CCOCC1.CCOC(C)=O.[Os](=O)(=O)(=O)=O>[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@@H:11]3[O:26][C@H:25]([CH2:27][O:28][CH2:29][C:30]4[CH:35]=[CH:34][C:33]([Cl:36])=[CH:32][C:31]=4[Cl:37])[C@@H:14]([O:15][CH2:16][C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][C:18]=4[Cl:24])[C@@:12]3([CH2:38][OH:44])[OH:13])[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: C[N+]1([O-])CCOCC1
Reactant: C=C[C@@]1(O)[C@H](OCc2ccc(Cl)cc2Cl)[C@@H](COCc2ccc(Cl)cc2Cl)O[C@H]1n1ccc2c(Cl)ncnc21
Agent: O=[Os](=O)(=O)=O
Agent: [BH4-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: OC[C@@]1(O)[C@H](OCc2ccc(Cl)cc2Cl)[C@@H](COCc2ccc(Cl)cc2Cl)O[C@H]1n1ccc2c(Cl)ncnc21
Reaction time: 14 h
Yield: 52.1 %

Procedure:
To a solution of the compound from Example 137, Step B (300 mg, 0.48 mmol) in 1,4-dioxane (5 mL) were added N-methylmorpholine-N-oxide (300 mg, 2.56 mmol) and osmium tetroxide (4% solution in water, 0.3 mL). The mixture was stirred in the dark for 14 h. The precipitate was removed by filtration through a celite plug, diluted with water (3×), and extracted with EtOAc. The EtOAc layer was dried over Na2SO4 and concentrated in vacuo. The oily residue was taken up in dichloromethane (5 mL) and stirred over NaIO4 on silica gel (3 g, 10% NaIO4) for 12 h. The silica gel was removed by filtration and the residue was evaporated and taken up in absolute ethanol (5 mL). The solution was cooled in an ice bath and sodium borohydride (300 mg, 8 mmol) was added in small portions. The resulting mixture was stirred at room temperature for 4 h and then diluted with EtOAc. The organic layer was washed with water (2×20 mL), brine (20 mL) and dried over Na2SO4. The solvent was evaporated and the residue purified by flash chromatography (SiO2, 2:1 hexanes/EtOAc) to give the title compound (160 mg, 0.25 mmol) as white flakes.
Reaction SMILES: [H-].[Na+].[N:3]1([CH2:7][CH2:8][CH2:9][OH:10])[CH2:6][CH2:5][CH2:4]1.[Br:11][C:12]1[CH:13]=[CH:14][C:15](F)=[N:16][CH:17]=1>C1COCC1>[N:3]1([CH2:7][CH2:8][CH2:9][O:10][C:15]2[CH:14]=[CH:13][C:12]([Br:11])=[CH:17][N:16]=2)[CH2:6][CH2:5][CH2:4]1
Reactant: OCCCN1CCC1
Reactant: Fc1ccc(Br)cn1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Brc1ccc(OCCCN2CCC2)nc1
Reaction time: 0.17 h
Yield: 121.7 %

Procedure:
Sodium hydride (1.364 g, 56.82 mmol) was added to 3-(azetidin-1-yl)propan-1-ol (2.62 g, 22.73 mmol) in THF (20 mL) at ambient temperature under an inert atmosphere and the reaction stirred for 10 minutes. 5-Bromo-2-fluoropyridine (2.0 g, 11.36 mmol) was added and the resulting solution stirred for 1 h before being quenched with water (20 mL) and extracted with EtOAc (5×50 mL). The organics were combined, dried over Na2SO4, filtered and concentrated in vacuo to afford the desired material (3.75 g, 122%) as a white solid. NMR Spectrum: 1H NMR (300 MHz, CDCl3) δ 1.80 (2H, m), 2.11 (2H, m), 2.55 (2H, t), 3.18 (4H, t), 4.328 (2H, t), 6.64 (1H, d), 7.62 (1H, dd), 8.16 (1H, d). Mass Spectrum: m/z (ES+)[M+H]+=271.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.[F:11][C:12]([F:39])([F:38])[C:13]([CH2:33][NH:34][CH2:35][CH2:36][CH3:37])([OH:32])[CH2:14][NH:15][C:16]1[CH:24]=[CH:23][CH:22]=[C:21]2[C:17]=1[CH:18]=[N:19][N:20]2[C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1>>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([N:34]([CH2:35][CH2:36][CH3:37])[CH2:33][C:13]([CH2:14][NH:15][C:16]1[CH:24]=[CH:23][CH:22]=[C:21]2[C:17]=1[CH:18]=[N:19][N:20]2[C:25]1[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=1)([OH:32])[C:12]([F:11])([F:39])[F:38])=[O:6]
Reactant: CCCNCC(O)(CNc1cccc2c1cnn2-c1ccc(F)cc1)C(F)(F)F
Reactant: O=C(O)c1ccccc1F
Product: CCCN(CC(O)(CNc1cccc2c1cnn2-c1ccc(F)cc1)C(F)(F)F)C(=O)c1ccccc1F

Procedure:
Prepared similarly to Example 1 from 2-fluorobenzoic acid and 1,1,1-trifluoro-3-{[1-(4-fluorophenyl)-1H-indazol-4-yl]amino}-2-[(propylamino)methyl]-2-propanol.
Reaction SMILES: Cl.Cl.[Cl:3][C:4]1[CH:19]=[CH:18][C:7]([CH2:8][O:9][CH2:10][C:11]2([NH2:17])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[CH:6][CH:5]=1.Cl[C:21]1[C:22]2[CH:29]=[CH:28][NH:27][C:23]=2[N:24]=[CH:25][N:26]=1.C(N(CC)CC)C>C(O)CCC>[Cl:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][O:9][CH2:10][C:11]2([NH2:17])[CH2:16][CH2:15][N:14]([C:21]3[C:22]4[CH:29]=[CH:28][NH:27][C:23]=4[N:24]=[CH:25][N:26]=3)[CH2:13][CH2:12]2)=[CH:18][CH:19]=1
Reactant: NC1(COCc2ccc(Cl)cc2)CCNCC1
Reactant: Clc1ncnc2[nH]ccc12
Agent: Cl
Solvent: CCCCO
Solvent: CCN(CC)CC
Product: NC1(COCc2ccc(Cl)cc2)CCN(c2ncnc3[nH]ccc23)CC1
Temperature: 100 °C
Reaction time: 17 h
Yield: 78.6 %

Procedure:
A degassed mixture of 4-(4-chloro-benzyloxymethyl)-piperidin-4-ylamine dihydrochloride (9.2 mg, 0.028 mmol), 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (5.9 mg, 0.035 mmol), triethylamine (36 uL, 0.2 mmol) and n-butanol (0.35 mL) was stirred at 100° C. for 17 h. The solvents were removed by evaporation. The crude mixture was purified on an SCX-II acid resin, eluting with methanol then 2M ammonia/methanol, and then by preparative TLC eluting with 10% methanol in dichloromethane, to give 4-(4-chloro-benzyloxymethyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-piperidin-4-ylamine (8.2 mg, 0.022 mmol, 78%). LC-MS (LCT2) m/z 372 [M+H+], Rt 3.19 min.
Reaction SMILES: Br[C:2]1[C:3]2[C:14]([Cl:15])=[CH:13][CH:12]=[CH:11][C:4]=2[S:5][C:6]=1[C:7]([O:9][CH3:10])=[O:8].[CH3:16][CH:17]([SH:19])[CH3:18].N12CCCN=C1CCCCC2>CN(C)C=O>[Cl:15][C:14]1[C:3]2[C:2]([S:19][CH:17]([CH3:18])[CH3:16])=[C:6]([C:7]([O:9][CH3:10])=[O:8])[S:5][C:4]=2[CH:11]=[CH:12][CH:13]=1
Reactant: CC(C)S
Reactant: COC(=O)c1sc2cccc(Cl)c2c1Br
Solvent: C1CCC2=NCCCN2CC1
Solvent: CN(C)C=O
Product: COC(=O)c1sc2cccc(Cl)c2c1SC(C)C
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A mixture of methyl 3-bromo-4-chlorobenzo[b]thiophene-2-carboxylate (0.62 g, 2.0 mmol) , 2-propanethiol (0.30 mL, 0.25 g, 3.2 mmol) , and 1,8-diazabicyclo[5.4.0]undec-7-ene (0.33 mL, 0.34 g, 2.2 mmol) in 5.0 mL of N,N-dimethylformamide is stirred at room temperature for 24 hours. The reaction mixture is partitioned between 150 mL of cold 1.0N HCl and 75 mL of dichloromethane, and the aqueous layer is extracted several times with fresh dichloromethane. The combined organic layers are washed with 1.0N HCl and brine, then dried (anhydrous sodium sulfate) and evaporated to yield methyl 4-chloro-3-[(1-methylethyl)thio]benzo[b]thiophene-2-carboxylate as an oil.
Reaction SMILES: O1CCCC1.[C:6]1([C:12]([NH:25][CH:26]2[C:44](=[O:45])[N:28]3[CH:29]([C:34]4[N:38](C(OCC)=O)[N:37]=[N:36][N:35]=4)[C:30]([CH3:33])([CH3:32])[S:31][C@H:27]23)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>O>[C:6]1([C:12]([NH:25][CH:26]2[C:44](=[O:45])[N:28]3[CH:29]([C:34]4[NH:35][N:36]=[N:37][N:38]=4)[C:30]([CH3:32])([CH3:33])[S:31][C@H:27]23)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: CCOC(=O)n1nnnc1C1N2C(=O)C(NC(c3ccccc3)(c3ccccc3)c3ccccc3)[C@H]2SC1(C)C
Solvent: O
Solvent: C1CCOC1
Product: CC1(C)S[C@@H]2C(NC(c3ccccc3)(c3ccccc3)c3ccccc3)C(=O)N2C1c1nnn[nH]1
Reaction time: 0.5 h

Procedure:
To a stirred mixture of 2 ml. of tetrahydrofuran and 4 ml. of water is added 150 mg. of 6-(triphenylmethylamino)-2,2-dimethyl-3-(1-[ethoxycarbonyl]tetrazol-5-yl)penam. The pH of the mixture is adjusted to 9.5, and stirring is continued at that pH for a further 30 minutes, at ambient temperature. The bulk of the tetrahydrofuran is removed by evaporation in vacuo, and the residue is portioned between water and ethyl acetate at pH 9. The ethyl acetate is removed and discarded. Fresh ethyl acetate is added and the pH is adjusted to 2.0. The ethyl acetate layer is removed, washed with water, dried using anhydrous sodium sulfate, and evaporated in vacuo to give the crude title compound.
Reaction SMILES: [CH3:1][C:2]([CH3:21])([CH3:20])[O:3][C:4](=[O:19])[NH:5][CH2:6][C:7](=[O:18])[NH:8][C@H:9]([C:14](OC)=[O:15])[CH2:10][CH2:11][S:12][CH3:13].[NH2:22][OH:23]>O1CCOCC1>[OH:23][NH:22][C:14](=[O:15])[C@@H:9]([NH:8][C:7](=[O:18])[CH2:6][NH:5][C:4](=[O:19])[O:3][C:2]([CH3:21])([CH3:20])[CH3:1])[CH2:10][CH2:11][S:12][CH3:13]
Reactant: COC(=O)[C@H](CCSC)NC(=O)CNC(=O)OC(C)(C)C
Reactant: NO
Solvent: C1COCCO1
Product: CSCC[C@H](NC(=O)CNC(=O)OC(C)(C)C)C(=O)NO
Yield: 28 %

Procedure:
A solution of (S)-methyl 12,12-dimethyl-7,10-dioxo-11-oxa-2-thia-6,9-diazatridecane-5-carboxylate (7 g, 21 mmol) in dioxane (120 mL) and hydroxylamine (50% in water, 80 mL) was stirred at room temperature for 4 hours. The solution was concentrated and extracted with ethyl acetate (200 mL). The organic layers were washed with 1N HCl, brine, and dried over sodium sulfate, filtered and concentrated to give a residue, which was purified on silica gel column (hexane:ethyl acetate, 1:1 to pure acetate) to give (S)-tert-butyl 2-(1-(hydroxyamino)-4-(methylthio)-1-oxobutan-2-ylamino)-2-oxoethylcarbamate (2 g, 28%). MS calcd for (C12H23N3O5S+H)+: 322.1; MS found: (M+H)+=322.0.
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10]([CH3:17])=[C:11]([Mg]Cl)[CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:18](=[O:20])=[O:19]>>[CH2:1]([O:8][C:9]1[C:10]([CH3:17])=[C:11]([CH:12]=[CH:13][CH:14]=1)[C:18]([OH:20])=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1c(OCc2ccccc2)cccc1[Mg]Cl
Reactant: O=C=O
Product: Cc1c(OCc2ccccc2)cccc1C(=O)O

Procedure:
The reaction of (3-benzyloxy-2-methylphenyl)magnesium chloride with carbon dioxide to give 3-benzyloxy-2-methylbenzoic acid can be carried out such that excess carbon dioxide gas is passed into the solution of the Grignard reagent (5) in THF. The alternative exists of initially introducing THF while passing in carbon dioxide gas and adding the Grignard solution. In this case, a suspension of the magnesium chloride salt of the acid (6) is formed first. The salt is hydrolyzed with sufficient aqueous mineral acid, preferably aqueous hydrochloric acid, such that the free acid (6) is completely liberated.
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[O:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([O:31][CH2:32]C(OC)=O)[C:26]=1[C:37](=O)[CH3:38])(=[O:3])[CH3:2].[Br:40][C:41]1[CH:48]=[CH:47][C:44]([CH:45]=O)=[CH:43][CH:42]=1.[OH-].[K+].Cl>C(O)C.O>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[O:24][C:25]1[C:26]2[C:37](/[CH:38]=[CH:45]/[C:44]3[CH:47]=[CH:48][C:41]([Br:40])=[CH:42][CH:43]=3)=[CH:32][O:31][C:27]=2[CH:28]=[CH:29][CH:30]=1)(=[O:3])[CH3:2]
Reactant: O=Cc1ccc(Br)cc1
Reactant: COC(=O)COc1cccc(O[C@@H]2O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]2OC(C)=O)c1C(C)=O
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CC(=O)OC[C@H]1O[C@@H](Oc2cccc3occ(/C=C/c4ccc(Br)cc4)c23)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 72 h
Yield: 31.2 %

Procedure:
To a suspension of 2′-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-6′-(methoxycarbonylmethoxy)acetophenone (0.55 g) and 4-bromobenzaldehyde (0.19 g) in ethanol (9 mL) were added water (3 mL) and potassium hydroxide (0.67 g), and the mixture was stirred at room temperature for three days. To the reaction mixture was added 2 mol/L hydrochloric acid (7 mL), and the resulting mixture was extracted with ethyl acetate twice. The extracts were combined and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. To the residue were added sodium acetate (1.97 g), acetic acid (5 mL) and acetic anhydride (2.08 mL), and the mixture was stirred at 115° C. overnight. The reaction mixture was cooled to room temperature and poured into water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and brine, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=2/1-3/2) to give the title compound (0.2 g).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([NH2:8])[C:5]([NH2:9])=[CH:4][N:3]=1.[N+:10]([C:13]1[CH:21]=[CH:20][C:16]([C:17](O)=O)=[CH:15][CH:14]=1)([O-:12])=[O:11].C([O-])([O-])=O.[K+].[K+]>>[N+:10]([C:13]1[CH:21]=[CH:20][C:16]([C:17]2[NH:9][C:5]3[CH:4]=[N:3][C:2]([NH2:1])=[CH:7][C:6]=3[N:8]=2)=[CH:15][CH:14]=1)([O-:12])=[O:11]
Reactant: Nc1cc(N)c(N)cn1
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: Nc1cc2nc(-c3ccc([N+](=O)[O-])cc3)[nH]c2cn1
Temperature: 180 °C
Yield: 42.3 %

Procedure:
2,4,5 Triaminopyridine (6, 0.660 g, 5.32 mmol), p-nitro benzoic acid (7, 0.888 mg 5.32 mmol) was taken in PPA (30 g) and heated at 180° C. for 7 h. The reaction mixture was cooled to room temperature and poured on to crushed ice. The excess PPA was neutralized carefully by addition of solid K2CO3 portion wise (caution) till effervescence ceased. The brownish green precipitate was filtered and washed with water and dried. The solid was taken in (CH2Cl2: MeOH:THF:NH4OH 50:30:17:3) mixture and filtered (repeated the process 3-4 times). The solvents were removed and the nitro amine precipitated with EtOAc to give 8 (0.575 g, 56%). 1H NMR (DMSO-d6; 500 MHz): δ11.10 (1H, brs), 8.77 (1H, s), 8.45-8.25 (4H m), 6.50 (1H, s), 5.67 (2H, brs); EIMS m/z: 256.4 (M+1) and 290 (M+Cl−);
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[CH:16]=2)[CH:8]=[CH:9][C:10]=1[C:11]([O:13][CH3:14])=[O:12])=[O:4].[C:22]([O:26][C:27]([N:29]([CH2:47][CH:48]=O)[CH2:30][C@H:31]([O:39][Si:40]([C:43]([CH3:46])([CH3:45])[CH3:44])([CH3:42])[CH3:41])[C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[CH:33]=1)=[O:28])([CH3:25])([CH3:24])[CH3:23]>>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([NH:21][CH2:48][CH2:47][N:29]([CH2:30][C@@H:31]([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([Cl:38])[CH:33]=3)[O:39][Si:40]([C:43]([CH3:44])([CH3:45])[CH3:46])([CH3:42])[CH3:41])[C:27]([O:26][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:28])[CH:16]=2)[CH:8]=[CH:9][C:10]=1[C:11]([O:13][CH3:14])=[O:12])=[O:4]
Reactant: CC(C)(C)OC(=O)N(CC=O)C[C@H](O[Si](C)(C)C(C)(C)C)c1cccc(Cl)c1
Reactant: COC(=O)c1ccc(-c2cccc(N)c2)cc1C(=O)OC
Product: COC(=O)c1ccc(-c2cccc(NCCN(C[C@H](O[Si](C)(C)C(C)(C)C)c3cccc(Cl)c3)C(=O)OC(C)(C)C)c2)cc1C(=O)OC

Procedure:
Electrospray MS (positive ion): (M+H) 697.6; from 3′-amino-[1,1′-biphenyl]-3,4-dicarboxylic acid dimethyl ester (580 mg) and (R)-[(tert-butoxycarbonyl)-[2-(tert-butyldimethylsilanoxy)-2-(3-chlorophenyl)ethyl]amino]-acetaldehyde (1.5 g).
Reaction SMILES: [C@@H:1]1([N:8]2[CH:15]=[CH:14][C:12](=O)[NH:11][C:9]2=[O:10])[O:7][C@H:4]([CH2:5][OH:6])[CH2:3][CH2:2]1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:17].O>N1C=CC=CC=1>[C@@H:1]1([N:8]2[CH:15]=[CH:14][C:12](=[S:17])[NH:11][C:9]2=[O:10])[O:7][C@H:4]([CH2:5][OH:6])[CH2:3][CH2:2]1
Reactant: O=c1ccn([C@H]2CC[C@@H](CO)O2)c(=O)[nH]1
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: O
Solvent: c1ccncc1
Product: O=c1[nH]c(=S)ccn1[C@H]1CC[C@@H](CO)O1
Yield: 95 %

Procedure:
When the 2',3'-dideoxy-uridine derivatives being raw materials in the invention are allowed to react with phosphorus pentasulfide in pyridine solvent, the amount of phosphorus pentasulfide is desirable to be not less than 0.5 times mol, preferably 1 to 2 times mol to 2',3'-dideoxy-uridine derivatives. In order to raise the yield of reaction further, it is preferable to add water to the reaction system and the amount of water to be added therefor is preferable to be 0.5 times mol to equivalent mol to phosphorus pentasulfide. Although the reaction proceeds without the addition of water, the reaction liquor becomes blackish brown and tarry substances are produced at this time resulting in the lowering in yield by several steps. The reaction completes by refluxing for 2 to 5 hours. After the completion of reaction, the pyridine solution is concentrated to distill off pyridine and the residue is extracted with chloroform. Thus, aimed 2',3'-dideoxy-4-thiouridine derivatives can be obtained easily in a yield of not less than 95 %. Following this, by eliminating the protecting groups with alkali or acid according to usual method, 2',3'-dideoxy-4-thio-uridine being the compound of the invention can be prepared in high yield and yet with ease.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH3:6][O:7][C:8]1[CH:9]=[C:10]([CH2:16][CH2:17][CH2:18][OH:19])[CH:11]=[CH:12][C:13]=1[O:14][CH3:15].CCN(CC)CC>C(Cl)Cl>[CH3:1][S:2]([O:19][CH2:18][CH2:17][CH2:16][C:10]1[CH:11]=[CH:12][C:13]([O:14][CH3:15])=[C:8]([O:7][CH3:6])[CH:9]=1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)Cl
Reactant: COc1ccc(CCCO)cc1OC
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(CCCOS(C)(=O)=O)cc1OC
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Under N2, methanesulfonyl chloride (129.7 g, 1.132 m, 87.6 cc) was added dropwise over 1-1.5 hours at -10° to 0° C. to a mechanically stirred solution of 3-(3,4-dimethoxyphenyl)-1-propanol (202 g, 1.03 mole) and Et3N (158.3 g, 1.56 mole, 218 cc) in CH2Cl2 (1.5 1) contained in a 5 1, 3-neck flask. The reaction mixture was stirred at 0° C. for 1 hour and then washed successively with icewater (1×700 cc), cold 3N HCl (1×700 cc), saturated NaHCO3 solution (1×700 cc) and brine (1×700 cc). The organic solution was dried (Na2SO4) and concentrated in vacuo to an orange syrup; yield: 282 g (100%).
Reaction SMILES: [OH-].[K+].C(O)C.Br[CH2:7][CH2:8][C:9]1([F:16])[C:11]([F:13])([F:12])[C:10]1([F:15])[F:14]>O>[CH:8]([C:9]1([F:16])[C:11]([F:13])([F:12])[C:10]1([F:15])[F:14])=[CH2:7]
Reactant: FC1(F)C(F)(F)C1(F)CCBr
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: C=CC1(F)C(F)(F)C1(F)F
Temperature: 70 °C
Reaction time: 2 h
Yield: 57.3 %

Procedure:
To a stirred solution of 18.0 g of KOH, 15 mL of ethanol and 20 mL of water was slowly added 24.0 g of 2-bromo-1-(pentafluorocyclopropyl)ethane at 70° C. During the addition, volatiles were collected in a -78° C. trap. After the addition was complete, the reaction mixture was stirred at 70° C. for an additional two hours until collection of all volatiles, which was distilled to give 9.1 g of product, bp 30° C. 19F NMR: -152.3 (dt, J =195.4 Hz, J=9.8 Hz, 2F), -156.0 (dm, J=195.6 Hz, 2F), -210.7 (t, J=7.7 Hz, 1F) . 1H NMR: 5.86-5.73 (m, 2H), 5.70-5.65 (m, 1H).
Reaction SMILES: C1C=CC=CC=1.[CH2:7]([OH:10])[CH2:8][OH:9].[CH3:11][C:12]1[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][C:13]=1[O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22](=[N:25][O:26][CH3:27])[CH:23]=O>[Cl-].[Na+].O.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH3:27][O:26][N:25]=[C:22]([CH:23]1[O:10][CH2:7][CH2:8][O:9]1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[CH2:15][O:14][C:13]1[CH:28]=[C:29]([CH3:32])[CH:30]=[CH:31][C:12]=1[CH3:11]
Reactant: CON=C(C=O)c1ccccc1COc1cc(C)ccc1C
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: c1ccccc1
Product: CON=C(c1ccccc1COc1cc(C)ccc1C)C1OCCO1
Reaction time: 2 h
Yield: 87.9 %

Procedure:
Benzene (4 ml), ethylene glycol (0.12 g, 2.0 mmol) and p-toluenesulfonic acid monohydrate (0.01 g, 0.05 mmol) were added to 2-(2,5-dimethylphenoxymethyl)-α-methoxyiminophenylacetaldehyde (0.3 g, 1.0 mmol), and the mixture was subjected to azeotropic dehydration for 2 hours. After completion of the reaction, half-saturated brine (100 ml) was added, and the mixture was extracted with dichloromethane (50 ml) twice. The extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetatein-hexane) to give 2-(2,5-dimethylphenoxymethyl)phenyl 1,3-dioxolan-2-yl ketone O-methyloxime (0.30 g, yield 87.9%) as colorless crystals. mp 136-137° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:23])[CH:5]([O:11][C:12]1[CH:20]=[C:19]2[C:15]([CH:16]=[C:17]([CH2:21][NH2:22])[NH:18]2)=[CH:14][CH:13]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].CCN(C(C)C)C(C)C.[C:33]1([S:39](Cl)(=[O:41])=[O:40])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(Cl)Cl>[CH2:9]([O:8][C:6](=[O:7])[CH:5]([O:11][C:12]1[CH:20]=[C:19]2[C:15]([CH:16]=[C:17]([CH2:21][NH:22][S:39]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)(=[O:41])=[O:40])[NH:18]2)=[CH:14][CH:13]=1)[C:4]([O:3][CH2:1][CH3:2])=[O:23])[CH3:10]
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: CCOC(=O)C(Oc1ccc2cc(CN)[nH]c2c1)C(=O)OCC
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)C(Oc1ccc2cc(CNS(=O)(=O)c3ccccc3)[nH]c2c1)C(=O)OCC
Temperature: 25 °C
Reaction time: 2 h

Procedure:
2-(2-Aminomethyl-1H-indol-6-yloxy)-malonic acid diethyl ester (80 mg, 0.2 5 mmol) is dissolved in DCM (2 ml). DIEA (87 □l, 0.50 mmol) is added. To the solution, benzenesulfonyl chloride (44 mg, 0.25 mmol) is added. The reaction is stirred at room temperature for two hours. The reaction mixture is concentrated and the residue is purified by chromatography (30% ethyl acetate in hexanes) to give the title compound.