Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [B-](F)(F)(F)F.[N+:6](=[O:8])=[O:7].N1C(C)=CC(C)=CC=1C.[CH3:18][C@H:19]([NH:22][C:23](=[S:41])[C@H:24]([NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:20][OH:21]>C(#N)C>[CH3:18][C@H:19]([NH:22][C:23](=[S:41])[C@H:24]([NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:20][O:21][N+:6]([O-:8])=[O:7]
Reactant: C[C@@H](CO)NC(=S)[C@@H](CC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C
Reactant: O=[N+]=O
Agent: F[B-](F)(F)F
Solvent: CC#N
Solvent: Cc1cc(C)nc(C)c1
Product: C[C@@H](CO[N+](=O)[O-])NC(=S)[C@@H](CC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C
Yield: 49.5 %

Procedure:
In 25 ml of dry acetonitrile were dissolved 1.24 g of nitronium tetrafluoroboron (85% content), 1.12 g of 2,4,6-collidine was added thereto with stirring under ice-cooling, and the mixture was stirred under ice-cooling for 30 minutes. Then, a solution obtained by dissolving 2.5 g of N-[(1S)-1-methyl-2-hydroxyethyl]-(2R)-2-t-butoxycarbonylamino-3-t-butoxycarbonylthiopropanamide in 25 ml of dry acetonitrile was added to the mixture and the resulting mixture was stirred at room temperature for 3 hours. Then, the solvent was distilled off under reduced pressure and the thus obtained residue was purified by silica gel column chromatography employing cyclohexane-ethyl acetate (4:1) as an eluent to obtain 1.39 g of the desired compound as pale yellow crystals.
Reaction SMILES: C([C:5](=[C:20]([CH2:24][CH2:25][OH:26])[CH2:21][CH2:22][OH:23])[O:6][SiH:7]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)(C)(C)C.[CH3:27][S:28](Cl)(=[O:30])=[O:29]>CCOCC>[CH3:27][S:28]([O:26][CH2:25][CH2:24][C:20](=[CH:5][O:6][Si:7]([C:20]([CH3:24])([CH3:21])[CH3:5])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[CH2:21][CH2:22][O:23][S:28]([CH3:27])(=[O:30])=[O:29])(=[O:30])=[O:29]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)C(O[SiH](c1ccccc1)c1ccccc1)=C(CCO)CCO
Solvent: CCOCC
Product: CC(C)(C)[Si](OC=C(CCOS(C)(=O)=O)CCOS(C)(=O)=O)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 9.5 h
Yield: 169.9 %

Procedure:
To a 0° C. ether (300 mL) solution of 3-(tertbutyldiphenylsilyloxymethylene)-pentane-1,5-diol (6.9 g, 19 mmol) was added methanesulfonyl chloride (4.3 mL, 56 mmol) followed by Et3 N (7.7 mL, 56 mmol). After 3-16 hours, gradually warming to ambient temperature, the reaction was washed with water, brine, dried over MgSO4, and concentrated to give the 1,5-bis(methanesulfonyloxy)-3-(tert-butyldiphenylsilyoxymethylene)-pentane 8.5g (90%) as a colorless oil that was used without further purification.
Reaction SMILES: C1C=CC=CC=1.[C:7]1([S:13]([C:16]2[CH:17]=[C:18]3[C:23](=[CH:24][CH:25]=2)[C:22](=[O:26])[CH2:21][CH2:20][CH2:19]3)(=[O:15])=[O:14])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.Br[CH:28](C)[C:29]([O:31][CH2:32]C)=[O:30]>O.[Zn]>[CH3:32][O:31][C:29](=[O:30])[CH2:28][C:22]1([OH:26])[C:23]2[C:18](=[CH:17][C:16]([S:13]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)(=[O:15])=[O:14])=[CH:25][CH:24]=2)[CH2:19][CH2:20][CH2:21]1
Reactant: O=C1CCCc2cc(S(=O)(=O)c3ccccc3)ccc21
Reactant: CCOC(=O)C(C)Br
Agent: [Zn]
Solvent: O
Solvent: c1ccccc1
Product: COC(=O)CC1(O)CCCc2cc(S(=O)(=O)c3ccccc3)ccc21
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A solution/suspension of anhydrous benzene (25 mL), powdered Zinc metal (0.505 g, 7.72 mmol), 12 (0.01 g) and 6-benzenesulfonyl-3,4-dihydro-2H-naphthalen-1-one was stirred for 10 minutes at room temperature. Ethyl bromopropionate (0.784 mL, 1.18 g, 7.07 mmol) was added and the reaction mixture was heated to reflux for 2.5 hours. The reaction mixture was allowed to cool, diluted with 300 mL of water and extracted twice with 250 mL of EtOAc. The combined organic layers were washed with water and saturated brine, dried (MgSO4) and evaporated under reduced pressure to yield (6-benzenesulfonyl-1-hydroxy-1,2,3,4-tetrahydro-naphthalen-1-yl)-acetic acid methyl ester. MS: 375 (M+H)+.
Reaction SMILES: [Cl-].[NH3+:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[Cl:13])[NH:9][C:8](=[O:14])[C:7](=[O:15])[NH:6]2.[CH:16]([CH:18]1[CH2:22][CH:21](OC)O[CH:19]1OC)=[O:17]>>[CH:16]([C:18]1[CH:22]=[CH:21][N:2]([C:3]2[CH:4]=[C:5]3[C:10](=[CH:11][C:12]=2[Cl:13])[NH:9][C:8](=[O:14])[C:7](=[O:15])[NH:6]3)[CH:19]=1)=[O:17]
Reactant: COC1CC(C=O)C(OC)O1
Reactant: [NH3+]c1cc2[nH]c(=O)c(=O)[nH]c2cc1Cl
Agent: [Cl-]
Product: O=Cc1ccn(-c2cc3[nH]c(=O)c(=O)[nH]c3cc2Cl)c1

Procedure:
16.5 mmol of 6-ammonio-7-chloro-2,3(1H,4H)-quinoxalinedione chloride were reacted with 16.5 mmol of 3-formyl-2,5-dimethoxytetrahydrofuran by the method of Example 5d.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].[H-].[Na+].[N+]([C:15]1[CH:16]=[C:17]([CH3:22])[N+:18]([O-:21])=[CH:19][CH:20]=1)([O-])=O>CN(C=O)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:15]2[CH:20]=[CH:19][N+:18]([O-:21])=[C:17]([CH3:22])[CH:16]=2)=[CH:4][C:3]=1[F:9]
Reactant: Cc1cc([N+](=O)[O-])cc[n+]1[O-]
Reactant: Oc1ccc(Br)c(F)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cc(Oc2ccc(Br)c(F)c2)cc[n+]1[O-]
Temperature: 180 °C
Reaction time: 0.17 h

Procedure:
4-Bromo-3-fluorophenol (0.5 g, 2.61 mmol) was added to a solution of sodium hydride (0.115 g, 2.90 mmol) in DMF (5 ml). After stiffing for 10 minutes 4-nitro-2-picoline N-oxide (0.37 g, 2.41 mmol) was added. The reaction mixture was heated at 180° C. for 1 hour under microwave irradiation. After cooling to room temperature the mixture was filtered through diatomaceous earth and this was thoroughly washed with EtOAc. The filtrate was washed with water (2×25 ml), the organic fraction was dried (Na2SO4) and the solvent evaporated in vacuo. The crude product was purified by column chromatography (silica gel; 0-3% methanol/DCM as eluent). The desired fractions were collected and evaporated in vacuo to yield intermediate D12 (0.33 g, 49%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[C:11]([CH3:14])[C:12]=1[CH3:13])[NH:9][CH2:8][C:7]1([CH2:17][CH2:16][CH2:15]1)[CH2:6]2.[Br:18][CH2:19][CH2:20]Br.C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C>[Br:18][CH2:19][CH2:20][N:9]1[C:10]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[C:12]([CH3:13])[C:11]=2[CH3:14])[CH2:6][C:7]2([CH2:15][CH2:16][CH2:17]2)[CH2:8]1
Reactant: COc1cc2c(c(C)c1C)NCC1(CCC1)C2
Reactant: BrCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc2c(c(C)c1C)N(CCBr)CC1(CCC1)C2

Procedure:
A solution of 6′-methoxy-7′,8′-dimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinoline] (1.12 g), 1,2-dibromoethane (2 mL) and Cs2CO3 (3.16 9) in DMF (7 mL) was heated in a bath of 110° C. for 6 hours. The mixture was cooled, water was added, and extracted with dichloromethane. The organic phase was then washed with brine, dried and evaporated. The residue was passed through a column (Hexane/EtOAc, 10:0.6) to give 1′-(2-bromoethyl)-6′-methoxy-7′,8′-dimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinoline] which was then added NaN3 (1.1 g) and dissolved in dichloromethane (7 mL). After heating the solution in a bath of 90° C. for 1 hour, the mixture was cooled, mixed with water and extracted with dichloromethane. The organic phase was washed with brine, dried and evaporated. The residue was passed through a column (Hexane/EtOAc, 10:0.5-10:0.6) to give 1′-(2-azidoethyl)-6′-methoxy-7′,8′-dimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinoline] (340 mg) as an oil. 1′-(2-azidoethyl)-6′-methoxy-7′,8′-dimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinoline] (340 mg) was dissolved in methanol (7 mL) and ethylacetate to which 50 mg Pd/C (10%) was added. The flask was then flushed evacuated and flushed with hydrogen. Under a balloon of hydrogen for 1 hour, the mixture was filtered and evaporated to give 2-(6′-methoxy-7′,8′-dimethyl-2′,4′-dihydro-1′H-spiro[cyclobutane-1,3′-quinoline]-1′-yl)ethanamine (278 mg) as an oil. 1H-NMR (300 MHz, C2D6O) δ=6.414 (s, 1H); 3.77 (s, 3H); 3.52 (s, 2H); 3.16-2.92 (m, 4H); 2.81 (s, 2H); 2.18 (s, 3H); 2.12 (s, 3H); 2.03-1.86 (m, 4H); 1.84-1.64 (m, 2H) ppm.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:10][S:11]([O:14][C:15]1[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([C:22]([CH3:26])([CH3:25])[CH2:23][OH:24])[CH:16]=1)(=[O:13])=[O:12]>C(OCC)C.[OH-].[Na+]>[CH3:10][S:11]([O:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:1](=[O:8])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:17]([C:22]([CH3:26])([CH3:25])[CH2:23][O:24][C:1](=[O:8])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:16]=1)(=[O:13])=[O:12]
Reactant: CC(C)(CO)c1cc(OS(C)(=O)=O)ccc1O
Reactant: O=C(Cl)c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Product: CC(C)(COC(=O)c1ccccc1)c1cc(OS(C)(=O)=O)ccc1OC(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Benzoyl chloride (5.6 g) in diethyl ether (50 ml) was added dropwise with vigorous stirring to a solution of 3-(2-hydroxy-1,1-dimethylethyl)-4-hydroxyphenyl methanesulphonate in aqueous sodium hydroxide solution (1.6 g in 100 ml water). The mixture was stirred for three hours at room temperature, then separated, and the ether solution washed with dilute sodium hydroxide solution followed by water. Drying over magnesium sulphate and running down gave 4.5 g of an oil. Crystallisation from ethanol gave 0.7 g of 3-(2-benzoyloxy-1,1-dimethyl-ethyl)-4-benzoyloxyphenyl methanesulphonate, m.p. 100°-101° C. Removal of the solvent from the mother liquors gave 2.5 g of 3-(2-benzoyloxy-1,1-dimethyl-ethyl)-4-hydroxyphenyl methanesulphonate as a viscous oil.
Reaction SMILES: [OH:1][C:2]([CH3:18])([CH3:17])[CH2:3][CH2:4][CH2:5][CH:6]([CH3:16])[CH2:7][CH:8]=[CH:9][C:10]([CH3:15])=[CH:11][C:12]([OH:14])=O.[CH2:19]([Li])[CH3:20].[Cl-].[NH4+]>C1C=CC=CC=1.CCOCC>[OH:1][C:2]([CH3:18])([CH3:17])[CH2:3][CH2:4][CH2:5][CH:6]([CH3:16])[CH2:7][CH:8]=[CH:9][C:10]([CH3:15])=[CH:11][C:12](=[O:14])[CH2:19][CH3:20]
Reactant: [Li]CC
Reactant: CC(C=CCC(C)CCCC(C)(C)O)=CC(=O)O
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Solvent: c1ccccc1
Product: CCC(=O)C=C(C)C=CCC(C)CCCC(C)(C)O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 3.35 g. of 11-hydroxy-3,7,11-trimethyldodeca-2,4-dienoic acid in 50 ml. ether at -20°C under nitrogen is added dropwise 59.1 ml. of a 0.67 molar solution of ethyllithium in benzene. The reaction mixture is allowed to warm to room temperature and is stirred overnight. The reaction mixture is then taken up in a mixture of ether and saturated aqueous ammonium chloride. The organic layer is separated, is washed with saturated aqueous ammonium chloride, 5% aqueous sodium bicarbonate, water, and saturated sodium chloride, is dried over calcium sulfate, and the solvent is removed to yield 13-hydroxy-5,9,13-trimethyltetradeca-4,6-dien-3-one which is purified by preparative thin layer chromatography (50% ether/hexane).
Reaction SMILES: [C:1]([O:4][C:5](=[O:7])[CH3:6])(=O)[CH3:2].[Cl:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH:11]=[CH:12][N:13]1[C:21](CO)=[C:20](C)[N:19]=[C:14]12>N1C=CC=CC=1>[C:5]([O:4][CH2:1][C:2]1[N:13]2[CH:12]=[CH:11][C:10]3[C:15]([C:14]2=[N:19][C:20]=1[CH3:21])=[CH:16][CH:17]=[CH:18][C:9]=3[Cl:8])(=[O:7])[CH3:6]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1nc2c3cccc(Cl)c3ccn2c1CO
Solvent: c1ccncc1
Product: CC(=O)OCc1c(C)nc2c3cccc(Cl)c3ccn12
Temperature: 25 °C
Reaction time: 24 h
Yield: 35.8 %

Procedure:
Acetic anhydride (0.71 g) was added dropwise to a suspension of 7-chloro-3-hydroxymethyl-2-methylimidazo[2,1-a]isoquinoline (1.43 g) in pyridine (14 ml) and the mixture was stirred at room temperature for 24 hours. The mixture was evaporated in vacuo and the residue was extracted with chloroform after an addition of water to it. The extract was washed with water, dried over magnesium sulfate, treated with activated charcoal and evaporated in vacuo. The crystalline residue was recrystallized from a mixture of ethyl acetate and diisopropyl ether to give 3-acetoxymethyl-7-chloro-2-methylimidazo[2,1-a]isoquinoline (0.6 g).
Reaction SMILES: [NH:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=2)[CH2:5][CH2:4][S:3]1.[C:17](Cl)(=[O:23])[O:18][CH2:19][CH2:20][CH2:21][CH3:22].C(N(CC)CC)C>O1CCCC1>[CH2:19]([O:18][C:17]([N:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:14])[F:15])[CH:8]=2)[CH2:5][CH2:4][S:3]1)=[O:23])[CH2:20][CH2:21][CH3:22]
Reactant: CCCCOC(=O)Cl
Reactant: N=C1SCCN1c1cccc(C(F)(F)F)c1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCCCOC(=O)N=C1SCCN1c1cccc(C(F)(F)F)c1
Yield: 40.5 %

Procedure:
A solution of N-(3-trifluoromethylphenyl)thiourea (6.1 g), dibromoethane (5.7 g) and anhydrous potassium carbonate (11.5 g) in acetone (60 ml) was refluxed for 1 day. The solvent was removed by distillation therefrom, and the residue was extracted with ethyl ether, washed with water, dried over anhydrous magnesium sulfate and subjected to column chromatography to give 7.5 g of 2-imino-3-(3-trifluoromethylphenyl)thiazolidine. The thus obtained 2-imino-3-(3-trifluoromethylphenyl)thiazolidine (1.0 g), n-butyl chlorocarbonate (0.61 g) and triethylamine (1.2 g) were dissolved in tetrahydrofuran, and the resultant solution was stirred at room temperature for 5 hours. The solvent was removed, and the residue was extracted with ethyl acetate, washed with water and dried over anhydrous magnesium sulfate. After removal of the solvent, the residue was subjected to column chromatography to give 0.57 g of 2-butoxycarbonylimino-3-(3-trifluoromethylphenyl)thiazolidine.
Reaction SMILES: Br[C:2]1[C:7]([N:8]([CH2:23][O:24][CH3:25])[S:9]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[C:14]([C:19]([F:22])([F:21])[F:20])[CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5]([Cl:26])=[CH:4][N:3]=1.C([Mg]Cl)(C)C.CN([CH:35]=[O:36])C>C1COCC1>[Cl:18][C:15]1[CH:16]=[CH:17][C:12]([S:9]([N:8]([C:7]2[C:2]([CH:35]=[O:36])=[N:3][CH:4]=[C:5]([Cl:26])[CH:6]=2)[CH2:23][O:24][CH3:25])(=[O:11])=[O:10])=[CH:13][C:14]=1[C:19]([F:22])([F:21])[F:20]
Reactant: COCN(c1cc(Cl)cnc1Br)S(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
Reactant: CN(C)C=O
Agent: CC(C)[Mg]Cl
Solvent: C1CCOC1
Product: COCN(c1cc(Cl)cnc1C=O)S(=O)(=O)c1ccc(Cl)c(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
To a stirred solution of N-(2-bromo-5-chloro-pyridin-3-yl)-4-chloro-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide (280 mg, 0.566 mmol) in anhydrous THF (3 mL) was added 2 M isopropylmagnesiumchloride in THF (700 L, 1.36 mmol) at 0° C. It was stirred at the same temperature for 20 minutes and then DMF (174 L, 1.36 mmol) was added in dropwise and the progress of the reaction was followed by LCMS. The reaction mixture was warmed to room temperature and stirred for 6 h. It was then quenched with saturated aqueous NH4Cl (2 mL), and extracted with EtOAc. The combined extracts were dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography to provide 4-Chloro-N-(5-chloro-2-formyl-pyridin-3-yl)-N-methoxymethyl-3-trifluoromethyl-benzenesulfonamide Mass spectrum m/z: 443.0 (M+H).
Reaction SMILES: C([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[N:20]=[C:19]([C:21]3[CH:26]=[C:25]([C:27]4[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:35])[F:34])=[CH:29][CH:28]=4)[CH:24]=[C:23]([CH3:37])[N:22]=3)[CH:18]=[CH:17][CH:16]=2)[CH:10]=1)(=[O:8])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[CH3:37][C:23]1[N:22]=[C:21]([C:19]2[CH:18]=[CH:17][CH:16]=[C:15]([C:11]3[CH:10]=[C:9]([S:6]([NH2:5])(=[O:7])=[O:8])[CH:14]=[CH:13][CH:12]=3)[N:20]=2)[CH:26]=[C:25]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([F:36])([F:34])[F:35])=[CH:29][CH:28]=2)[CH:24]=1
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2cccc(-c3cccc(S(=O)(=O)NC(C)(C)C)c3)n2)n1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)cc(-c2cccc(-c3cccc(S(N)(=O)=O)c3)n2)n1
Temperature: 25 °C
Reaction time: 15 h
Yield: 55 %

Procedure:
To a cooled and stirred solution of N-tert-butyl-3-[6′-methyl-4′-(4-trifluoromethylphenyl)-[2,2′]bipyridinyl-6-yl]-benzenesulfonamide (example 261) (0.570 g, 1.085 mmol) in dichloromethane (10 mL) was added TFA (10 mL) and the reaction mixture was allowed to stir at room temperature for 15 h. The mixture was evaporated to dryness and saturated NaHCO3 solution (5 mL), diethyl ether and heptane were added. The mixture was stirred at room temperature for 1 h, the precipitate was collected by filtration, washed with water and heptane/diethyl ether and dried to yield the title compound as a white solid (0.28 g, 55%). MS (ISP) 468.2 [(M+H)+]; mp 250° C.
Reaction SMILES: [CH2:1]([CH:4]([CH2:15][CH:16]=[CH2:17])[CH2:5][O:6][SiH2:7][C:8]1[CH:13]=[CH:12][C:11](I)=[CH:10][CH:9]=1)[CH:2]=[CH2:3].C([Mg]Cl)(C)C.C(C(CC=C)CO[SiH2]C1C=CC([Mg]Cl)=CC=1)C=C.[CH3:41][Sn:42](Cl)([CH3:44])[CH3:43]>O.C1COCC1>[CH2:1]([CH:4]([CH2:15][CH:16]=[CH2:17])[CH2:5][O:6][SiH2:7][C:8]1[CH:13]=[CH:12][C:11]([Sn:42]([CH3:44])([CH3:43])[CH3:41])=[CH:10][CH:9]=1)[CH:2]=[CH2:3]
Reactant: C=CCC(CC=C)CO[SiH2]c1ccc(I)cc1
Reactant: C[Sn](C)(C)Cl
Agent: C=CCC(CC=C)CO[SiH2]c1ccc([Mg]Cl)cc1
Agent: CC(C)[Mg]Cl
Solvent: C1CCOC1
Solvent: O
Product: C=CCC(CC=C)CO[SiH2]c1ccc([Sn](C)(C)C)cc1
Temperature: 25 °C
Reaction time: 13 h
Yield: 96 %

Procedure:
At first, a THF solution (2 mL) of the 4-(diallylethoxysilyl)iodobenzene (202 mg, 0.56 mmol) obtained in Example 2 was added dropwise with 2 mol/L of i-PrMgCl (0.59 mL (solvent: THF), 1.18 mmol) at −30° C. Then, the resultant solution was stirred under a nitrogen atmosphere at −30° C. for 1.5 hours to obtain a THF solution containing 4-(diallylethoxysilyl)phenylmagnesium chloride (Grignrad solution). Subsequently, the obtained Grignrad solution was added dropwise with 1 mol/L of trimethyl tin chloride (Me3SnCl: 1.18 mL (solvent: THF), 1.18 mmol) at −30° C. to obtain a reaction mixture. Thereafter, the reaction mixture was stirred under a nitrogen atmosphere at room temperature for 13 hours, and added with distilled water to terminate the reaction. After that, the organic layer was separated from the reaction mixture, and the aqueous layer was extracted with ether to collect the organic layer. Subsequently, the organic layer thus collected was washed with sat.NaHCO3 and sat.NaCl, dried with MgSO4, filtered, and concentrated to obtain a crude product. Thereafter, the crude product thus obtained was separated and purified by silica gel column chromatography (hexane/EtOAc=5/1), and thereby 4-(diallylethoxysilyl)phenyl-trimethyltin was obtained (214 mg, 96% yield).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([N+:10]([O-])=O)[C:7]([C:13]([F:16])([F:15])[F:14])=[CH:6][C:5]=1[NH:17][C:18](=[O:20])[CH3:19].[H][H]>CO.[Pd]>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([NH2:10])[C:7]([C:13]([F:16])([F:15])[F:14])=[CH:6][C:5]=1[NH:17][C:18](=[O:20])[CH3:19]
Reactant: COC(=O)c1cc([N+](=O)[O-])c(C(F)(F)F)cc1NC(C)=O
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1cc(N)c(C(F)(F)F)cc1NC(C)=O
Yield: 103.1 %

Procedure:
A solution of 1.7 g (5.55 mmol) of 2-acetylamino-5-nitro-4-trifluoromethyl-benzoic acid methyl ester in 29 ml of methanol is treated with 250 mg of Pd/C (10%) and the mixture stirred under 5 bars of hydrogen for 20 minutes. The mixture is filtered and the filtrate concentrated in vacuo to give 1.58 g (quantitative) of 2-acetylamino-5-amino-4-trifluoromethyl-benzoic acid methyl ester as yellow crystals, m.p. 143-152° C.
Reaction SMILES: [O:1]=[C:2]1[C@H:6]([NH:7][C:8]([C:10]2[C:14]([CH3:15])=[C:13](/[CH:16]=[C:17]3\[C:18](=[O:27])[NH:19][C:20]4[C:25]\3=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[NH:12][C:11]=2[CH3:28])=[O:9])[CH2:5][O:4][NH:3]1.[H-].[Na+].Br[CH2:32][C:33]([N:35]([CH3:37])[CH3:36])=[O:34]>>[CH3:36][N:35]([CH3:37])[C:33]([CH2:32][N:3]1[C:2](=[O:1])[C@H:6]([NH:7][C:8]([C:10]2[C:14]([CH3:15])=[C:13](/[CH:16]=[C:17]3\[C:18](=[O:27])[NH:19][C:20]4[C:25]\3=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[NH:12][C:11]=2[CH3:28])=[O:9])[CH2:5][O:4]1)=[O:34]
Reactant: CN(C)C(=O)CBr
Reactant: Cc1[nH]c(/C=C2\C(=O)Nc3ccc(F)cc32)c(C)c1C(=O)N[C@@H]1CONC1=O
Agent: [H-]
Agent: [Na+]
Product: Cc1[nH]c(/C=C2\C(=O)Nc3ccc(F)cc32)c(C)c1C(=O)N[C@@H]1CON(CC(=O)N(C)C)C1=O
Yield: 13.6 %

Procedure:
To the solution of 42b (1.0 eq.) cooled on ice bath was added NaH (4.0 or 1.5 eq.). The resulting mixture was stirred for an hour and was then added 2-bromo-N,N-dimethylacetamide (1.0 eq.), the reaction mixture was stirred at room temperature for several hours. LC/MS detection was applied to determine completion of the reaction. DMF was evaporated under reduced pressure and the residue was precipitated with 5% diethylamine/methanol under sonication. The solid was collected by filtration, washed with methanol twice, and further purified by column chromatography to obtain title compound (30 mg, 13.6% yield) as orange solids: 1H NMR (300 MHz, DMSO-d6): δ=13.73 (s, 1H), 10.93 (s, 1H), 8.05-8.08 (d, 1H), 7.74-7.80 (m, 2H), 6.82-6.97 (m, 2H), 5.06-5.15 (q, 1H), 4.39-4.58 (m, 3H), 4.05-4.11 (q, 1H), 2.97 (s, 3H), 2.84 (s, 3H), 2.44-2.47 (ds, 6H). LC/MS: 468.2 [M−H]+.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:5][S:6][CH2:7][CH:8]1[CH2:10][CH2:9]1)[CH2:3][OH:4].CO[CH:13](O)[C:14]([F:17])([F:16])[F:15].O>C1(C)C=CC=CC=1>[CH:8]1([CH2:7][S:6][CH2:5][CH:2]2[CH2:3][O:4][CH:13]([C:14]([F:17])([F:16])[F:15])[NH:1]2)[CH2:10][CH2:9]1
Reactant: COC(O)C(F)(F)F
Reactant: N[C@H](CO)CSCC1CC1
Solvent: Cc1ccccc1
Solvent: O
Product: FC(F)(F)C1NC(CSCC2CC2)CO1
Yield: 86.6 %

Procedure:
A solution of 2(R)-amino-3-cyclopropylmethylsulfanylpropan-1-ol (3.2 g, 20.0 mmol), prepared as described in Example 2, Steps 1 and 2 above, and trifluoroacetaldehyde methyl hemiacetal (2.6 g, 20.0 mmol) in toluene (20 mL) was heated at reflux with Dean Stark trapping of water for 24 h. The reaction mixture was concentrated to give 4-cyclopropylmethylsulfanylmethyl-2-trifluoromethyloxazolidine (4.18 g) as a pale yellow oil.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH:5]([OH:11])[CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.[OH-].[Na+]>Cl>[Cl:1][CH2:2][CH2:3][CH2:4][CH:5]([O:11][CH:13]1[CH2:14][CH2:15][CH2:16][CH2:17][O:12]1)[CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: C1=COCCC1
Reactant: CCCCCC(O)CCCCl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: CCCCCC(CCCCl)OC1CCCCO1
Reaction time: 2 h

Procedure:
To a stirred solution of 1-chloro-4-hydroxynonane (Example A, Step 2) (11.0 g., 0.062 mole) and dihydropyrane (5.2 g., 0.062 mole) cooled in an ice bath is added 5 drops of hydrochloric acid (conc.). A slight exothermic reaction is noted and when this is complete the reaction is allowed to come to room temperature, then stand for 2 hours. At the end of this period several pellets of sodium hydroxide are added and the reaction is distilled in vacuo. The yield of 1-chloro-4-(2-tetrahydropyranyloxy)nonane is 12.5 g. (77%), boiling 96°-102°/0.1 mm. Upon redistillation a boiling point of 90°-92°/0.1 mm. is obtained.
Reaction SMILES: [CH3:1][C:2]([CH3:15])=[CH:3][CH2:4][NH:5][C:6]1[N:14]=[CH:13][N:12]=[C:11]2[C:7]=1[NH:8][CH:9]=[N:10]2.[Br:16][CH2:17][CH2:18]Br.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C>CS(C)=O>[CH3:1][C:2]([CH3:15])=[CH:3][CH2:4][NH:5][C:6]1[N:14]=[CH:13][N:12]=[C:11]2[C:7]=1[N:8]=[CH:9][N:10]2[CH2:18][CH2:17][Br:16]
Reactant: BrCCBr
Reactant: CC(C)=CCNc1ncnc2nc[nH]c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: CC(C)=CCNc1ncnc2c1ncn2CCBr
Yield: 70 %

Procedure:
Mixture of 6-[(3-methylbut-2-en-1-yl)amino]purine (2 g, 9.8 mmol), 1,2-dibromoethane (12.94 g, 6 ml, 69 mmol) and K2CO3 (2.5 g, 24 mmol) was stirred in 50 ml DMSO for 12 h. Reaction mixture was poured onto drift ice and after ice dissolution 30 ml ethyl acetate was added. Ethyl acetate layer was purified by charcoal and SiO2 and then it was evaporated in vacuo. The pure product was recrystallised from methanol; yellow solid was obtained. Yield: 70%. 1H NMR (DMSO-d6): 1.75 (3H, s), 1.59 (3H, s), 4.12 (2H, t, J=5.76), 4.10 (2H, s (br)), 4.6 (2H, t, J=5.76), 5.3 (1H, t, J=6.57), 8.1 (1H, s (br)), 8.3 (1H, s).