Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [ClH:1].[N+:2]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9][NH2:10])=[CH:7][CH:6]=1)([O-:4])=[O:3].C(N(C(C)C)CC)(C)C.[NH:22](C(OC(C)(C)C)=O)[CH2:23][C:24]([O:26]N1C(=O)CCC1=O)=[O:25]>ClCCl>[NH2:22][CH2:23][CH:24]([OH:26])=[O:25].[ClH:1].[N+:2]([C:5]1[CH:6]=[CH:7][C:8]([CH2:9][NH-:10])=[CH:11][CH:12]=1)([O-:4])=[O:3]
Reactant: CC(C)(C)OC(=O)NCC(=O)ON1C(=O)CCC1=O
Reactant: NCc1ccc([N+](=O)[O-])cc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: [NH-]Cc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
4-Nitrobenzylamine hydrochloride (1 g; 5.3 mmol) and diisopropylethylamine (1.8 ml; 10.6 mmol) were dissolved in 70 ml of dichloromethane at RT. BOC-Gly-OSu (1.44 g; 5.3 mmol) was added and the solution was stirred at RT overnight. After evaporating the solvent in a rotary evaporator, the residue was taken up in 50 ml of ethyl acetate and extracted in each case 2× with 5% KHSO4, 5% NaHCO3 and distilled water. The organic phase was dried over Na2SO4, the solvent was evaporated and toluene was then added and evaporated in a rotary evaporator. The resultant oil was dissolved, without further work-up, directly in 15 ml of 4M HCl/dioxane and stirred at RT. After a short time, the product starts to precipitate. After 1 h, the solvent was evaporated, the solid was suspended in 100 ml of ethyl acetate, filtered off and washed with petroleum ether. The white solid was dried under vacuum.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:6][C:7]3[C:12]([C:13]=2[CH:14]=1)=[CH:11][CH:10]=[CH:9][CH:8]=3.[C:15](OC(=O)C)(=[O:17])[CH3:16]>OS(O)(=O)=O.C(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:15](=[O:17])[CH3:16])[C:7]3[C:12]([C:13]=2[CH:14]=1)=[CH:11][CH:10]=[CH:9][CH:8]=3
Reactant: Brc1ccc2[nH]c3ccccc3c2c1
Reactant: CC(=O)OC(C)=O
Agent: O=S(=O)(O)O
Solvent: ClC(Cl)Cl
Product: CC(=O)n1c2ccccc2c2cc(Br)ccc21
Temperature: 25 °C
Yield: 52.1 %

Procedure:
A solution of 3-bromo-9H-carbazole (10.00 g, 40.6 mmol), acetic anhydride (8.30 g, 81 mmol) together with 2 drops of H2SO4 in chloroform (150 mL) was refluxed overnight. After cooling to room temperature, the solution was washed with water. Upon evaporation of the solvent, the crude product was purified by crystallization from hexane/DCM and hexane/EtOAc to yield 1-(3-bromo-9H-carbazol-9-yl)ethanone (6.1 g, 51% yield) as a light yellow solid.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C@@H:11](O)[CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.CS(Cl)(=O)=O.[N-:40]=[N+:41]=[N-:42].[Na+]>C(Cl)Cl>[N:40]([C@H:11]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH3:10])=[N+:41]=[N-:42]
Reactant: CCCCCCCCCCCCCCC[C@H](O)[C@H](C)NC(=O)OC(C)(C)C
Reactant: [N-]=[N+]=[N-]
Agent: CS(=O)(=O)Cl
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCCCCCCCCCC[C@@H](N=[N+]=[N-])[C@H](C)NC(=O)OC(C)(C)C
Reaction time: 2 h
Yield: 50.7 %

Procedure:
To a cold (0° C.) solution of alcohol 94 (48 mg, 0.12 mmol) in CH2Cl2 (1.25 mL), Et3N (52 μL, 0.37 mmol) and MsCl (24 μL, 0.31 mmol) were added. After stirring for 2 h, the mixture was quenched with H2O (10 mL), extracted with CH2Cl2 (3×10 mL), dried over Na2SO4 and concentrated in vacuo. The crude mesylate was dissolved in DMF (0.65 mL) and NaN3 (40.5 mg, 0.62 mmol) was added. The mixture was stirred at 120 C. for 3 h and then quenched with H2O (10 mL), extracted with Et2O (3×10 mL), dried over Na2SO4 and concentrated in vacuo. The crude was purified by column chromatography on silica (hexane/EtOAc 10:1 to 5:1) to obtain azide 95 as a colorless oil (25 mg, 49% yield).
Reaction SMILES: [Li][CH2:2]CCC.CCCCCC.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH:20]2[O:25][C@@H:24]([CH:26]=O)[C:23]([CH3:29])([CH3:28])[CH2:22][O:21]2)=[CH:16][CH:15]=1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[CH3:29][C:23]1([CH3:28])[CH2:22][O:21][CH:20]([C:17]2[CH:16]=[CH:15][C:14]([O:13][CH3:12])=[CH:19][CH:18]=2)[O:25][C@H:24]1[CH:26]=[CH2:2]
Reactant: [Li]CCCC
Reactant: COc1ccc(C2OCC(C)(C)[C@H](C=O)O2)cc1
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: C=C[C@@H]1OC(c2ccc(OC)cc2)OCC1(C)C
Yield: 81 %

Procedure:
Following the general procedure for the methylenation by Wittig-olefination of Description 8, a phosphorous ylide generated from 73.4 g (205.5 mmol) of methyltriphenylphosphonium bromide and 125.7 mL of 1.6 M n-BuLi in hexane (201.1 mmol) in 440 mL of anhydrous tetrahydrofuran (THF), was reacted with 25.0 g (100.0 mmol) of (4R)-2-(4-methoxyphenyl)-5,5-dimethyl-1,3-dioxan-4-carbaldehyde (8b). Aqueous work-up followed by purification using column chromatography with mixtures of diethyl ether (Et2O), ethyl acetate (EtOAc), and hexanes (Hxn) as eluent (Et2O/Hxn=1:25→EtOAc/Hxn=1:9) provided 20.0 g (81% yield) of the title compound (8c) as a yellow liquid. Rf=0.42 (MTBE/Hxn=1:9). 1H NMR (400 MHz, CHCl3): δ=0.81 (s, 3H), 1.15 (s, 3H), 3.65 (d, J=10.8 Hz, 1H), 3.76 (d, J=11.2 Hz, 1H), 3.81 (s, 3H), 4.03 (d, J=6.4 Hz, 1H), 5.23-527 (m, 1H), 5.29-5.35 (m, 1H), 5.50 (s, 1H), 5.86 (ddd, J=17.2, 10.8, 6.4 Hz, 1H), 6.87-6.92 (m, 2H), 7.43-7.48 (m, 2H) ppm. MS (ESI) m/z: 249.1 (M+H)+. The analytical data was consistent with the proposed structure and with the data given in the literature for the compound (Blakemore, et al., J. Org. Chem. 2005, 70, 5449-5460; and Shiina, et al., Bull Chem. Soc. Jpn. 2001, 74, 113-122).
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[C:11](=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7][C:5]=2[N:6]=1.[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([O:24][CH3:25])=[C:18](NC(N)=S)[CH:19]=1>>[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([O:24][CH3:25])=[C:16]([NH:1][C:2]2[S:3][C:4]3[C:11](=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7][C:5]=3[N:6]=2)[CH:15]=1
Reactant: Nc1nc2c(s1)C(=O)CCCC2
Reactant: COc1ccc(Cl)cc1NC(N)=S
Product: COc1ccc(Cl)cc1Nc1nc2c(s1)C(=O)CCCC2
Yield: 26 %

Procedure:
Following the procedure described for 26z by condensing 5-chloro-2-methoxyphenylthiourea gave 30z (light brown solid; 26% for two steps). 1H NMR (600 MHz, DMSO-d6): δ 7.81 (d, J=2.4 Hz, 1H), 7.75 (dd, J=9 Hz, 2.4 Hz, 1H), 7.42 (d, J=9 Hz, 1H), 3.83 (s, 3H), 2.84-2.75 (m, 2H), 2.58-2.52 (m, 1H), 2.33-2.28 (m, 1H), 1.90-1.74 (m, 4H). 13C NMR (150 MHz, DMSO-d6): δ 194.4, 169.8, 154.5, 148.9, 134.1, 130.2, 125.7, 122.6, 121.7, 116.3, 57.6, 42.9, 30.5, 24.4, 21.5.
Reaction SMILES: [NH2:1][C:2]1[C:11]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:18]3[C:25]([CH3:26])=[CH:24][CH:23]=[CH:22][C:19]=3[C:20]#[N:21])[CH:8]=2)[N:3]=1.[CH2:27]([Mg]Br)[CH2:28][CH3:29].C1COCC1>>[NH:21]=[C:20]([C:19]1[CH:22]=[CH:23][CH:24]=[C:25]([CH3:26])[C:18]=1[C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([NH2:1])[C:11]([N:12]1[CH2:13][CH2:14][O:15][CH2:16][CH2:17]1)=[CH:10]2)[CH2:27][CH2:28][CH3:29]
Reactant: Cc1cccc(C#N)c1-c1ccc2nc(N)c(N3CCOCC3)cc2c1
Reactant: CCC[Mg]Br
Solvent: C1CCOC1
Product: CCCC(=N)c1cccc(C)c1-c1ccc2nc(N)c(N3CCOCC3)cc2c1
Temperature: 60 °C

Procedure:
To a sealed vessel containing 2-(2-amino-3-morpholinoquinolin-6-yl)-3-methylbenzonitrile (0.040 g, 0.116 mmol) under N2 atmosphere was added a solution of propylmagnesium bromide, 2.0M in THF (0.232 mL, 0.465 mmol) via syringe at ambient temperature. The mixture was sonicated until all solids were in solution and then warmed vessel to 60° C. for 7 h. The mixture was concentrated, diluted with MeOH and purified on HPLC (10-100% MeCN/H2O with 0.1% TFA modifier) to afford 6-(2-(1-iminobutyl)-6-methylphenyl)-3-morpholinoquinolin-2-amine as white solid. MS (ESI, pos. ion) m/z: 389 (M+1).
Reaction SMILES: [NH2:1][C:2]1([CH:8]([C:10]2[CH:15]=[C:14]([Cl:16])[CH:13]=[C:12]([Cl:17])[CH:11]=2)[OH:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.N1C=CC=CC=1.[C:24]1([CH3:34])[CH:29]=[CH:28][C:27]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:25]=1.Cl>C(Cl)Cl>[Cl:17][C:12]1[CH:11]=[C:10]([CH:8]([OH:9])[C:2]2([NH:1][S:30]([C:27]3[CH:28]=[CH:29][C:24]([CH3:34])=[CH:25][CH:26]=3)(=[O:32])=[O:31])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]2)[CH:15]=[C:14]([Cl:16])[CH:13]=1
Reactant: NC1(C(O)c2cc(Cl)cc(Cl)c2)CCCCC1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)NC2(C(O)c3cc(Cl)cc(Cl)c3)CCCCC2)cc1
Temperature: 35 °C

Procedure:
To a stirred solution of (1-amino-cyclohexyl)-(3,5-dichloro-phenyl)-methanol and pyridine (100 μL, 1.24 mmol) in CH2Cl2 (4 mL) was added p-toluenesulfonyl chloride. The mixture was heated at ca. 35° C. for 8 hours. The mixture was applied to a 10 mL Chem Elut cartridge pre-wetted with 5% aqueous HCl (5 mL) and eluted with CH2Cl2 (25 mL). The eluate was applied to a second Chem Elut cartridge pre-wetted with saturated aqueous NaHCO3. The eluate from the second cartridge was evaporated to leave N-{1-[(3,5-dichloro-phenyl)-hydroxy-methyl]-cyclohexyl}-4-methyl-benzenesulfonamide (139 mg) as an oil. 1H NMR (500 MHz, CDCl3) δ(ppm): 7.7 (d, 2H), 7.2 (s, 2H), 7.15 (d, 2H), 7.1 (s, 1H), 4.82 (s, 1H), 4.16 (s, 1H), 2.33 (s, 3H), 0.9-1.9 (m, 10H).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[C:4]([CH2:9][C:10]([CH3:12])=[CH2:11])[CH:3]=1.II>C(Cl)Cl.C(OC)(C)(C)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[O:8][C:10]([CH3:12])([CH3:11])[CH2:9][C:4]=2[CH:3]=1
Reactant: C=C(C)Cc1cc(Br)ccc1O
Agent: II
Solvent: COC(C)(C)C
Solvent: ClCCl
Product: CC1(C)Cc2cc(Br)ccc2O1
Temperature: 25 °C
Reaction time: 48 h
Yield: 89 %

Procedure:
To a solution of 4-bromo-2-(2-methylallyl)phenol (7) (4.5 g, 19.8 mmol) in CH2Cl2 (250 mL) was added iodine (1.3 g, 4.95 mmol) and the mixture stirred at room temperature for 48 h. The mixture was then diluted with methyl tert-butyl ether (100 mL) and washed with H2O (50 mL), brine (50 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, eluting with 5% ethyl acetate in hexanes) to give the title compound (8) (4.0 g, 88%) as yellow liquid. 1H NMR (CDCl3, 400 MHz) δ 7.24 (s, 1H), 7.20 (d, J=8.4 Hz, 1H), 6.61 (d, J=8.4 Hz, 1H), 3.00 (s, 2H), 1.47 (s, 6H); MS (ESI, M+H+) C10H12BrO, calcd. 227.1. found 227.0, 229.0.
Reaction SMILES: Br.Cl[C:3]1[CH:4]=[CH:5][C:6]2[N:7]([C:9]([NH2:12])=[N:10][N:11]=2)[N:8]=1.[CH2:13]([NH:15][CH2:16][CH3:17])[CH3:14]>O>[CH2:13]([N:15]([CH2:16][CH3:17])[C:3]1[CH:4]=[CH:5][C:6]2[N:7]([C:9]([NH2:12])=[N:10][N:11]=2)[N:8]=1)[CH3:14]
Reactant: Nc1nnc2ccc(Cl)nn12
Reactant: CCNCC
Agent: Br
Solvent: O
Product: CCN(CC)c1ccc2nnc(N)n2n1

Procedure:
6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-ylamine hydrobromide (W2.001; 150 mg) was initially charged in water (5 ml) and admixed with diethylamine (814 μl) while stirring. Thereafter, the mixture was heated to reflux for 16 h and then further diethylamine (407 μl) was added. After refluxing for a further 12 h, the mixture was freed of the solvent, admixed with water and extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and, after the desiccant had been filtered off, dried under reduced pressure. 67 mg of the title compound were obtained.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]([Cl:11])=[CH:9][CH:10]=1)=[O:5])[CH3:2].S(Cl)([Cl:15])(=O)=O.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(#N)C>[CH2:1]([O:3][C:4]([C:6]1[S:7][C:8]([Cl:11])=[C:9]([Cl:15])[CH:10]=1)=[O:5])[CH3:2]
Reactant: O=S(=O)(Cl)Cl
Reactant: CCOC(=O)c1ccc(Cl)s1
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CC#N
Product: CCOC(=O)c1cc(Cl)c(Cl)s1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
5-Chloro-2-thiophenecarboxylic acid (6.50 g) was dissolved in N,N-dimethylformamide (30 ml), and ethyl iodide (3.2 ml) and potassium carbonate (5.52 g) were added. The mixture was stirred at room temperature for 15 hours, poured into water and extracted with diethyl ether. The extract was washed with 5% aqueous potassium hydrogen sulfate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 5-chloro-2-thiophenecarboxylic acid ethyl ester (5.27 g). 5-Chloro-2-thiophenecarboxylic acid ethyl ester (2.23 g) was dissolved in acetonitrile (30 ml), and sulfuryl chloride (1.4 ml) in acetonitrile (20 ml) was added dropwise. The mixture was stirred at room temperature for 48 hours, and 10% aqueous sodium thiosulfate (100 ml) was added. The mixture was stirred at room temperature for 2 hours and extracted with diethyl ether. The extract was washed with saturated aqueous sodium chloride, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography. The desired fractions were concentrated under reduced pressure to give 4,5-dichloro-2-thiophenecarboxylic acid ethyl ester (6.21 g). 4,5-Dichloro-2-thiophenecarboxylic acid ethyl ester (6.21 g) was dissolved in a mixture of ethanol (25 ml) and tetrahydrofuran (25 ml), and 1N aqueous sodium hydroxide (50 ml) was added. The mixture was stirred at 60° C. for 15 hours and washed with diethyl ether. The aqueous layer was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 4,5-dichloro-2-thiophenecarboxylic acid (2.14 g) as crystals.
Reaction SMILES: [C:1]1([CH2:7][C:8]([OH:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:11]O>>[C:1]1([CH2:7][C:8]([O:10][CH3:11])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CO
Reactant: O=C(O)Cc1ccccc1
Product: COC(=O)Cc1ccccc1

Procedure:
Dissolved 13 g (0.1 mol) of phenylacetic acid in 500 ml of anhydrous methanol. Introduced HC1 gas, while refluxing for 3 hours. The solvent was then removed by evaporation. Dissolved the ester in benzene, which was successively washed with water and 10% NaOH. The organic layer was dehydrated with anhydrous magnesium sulfate. The solvent was again removed by evaporation. Methyl phenylacetate was finally purified by column chromatography employing silica gel chloroform system. The solvent was removed by evaporation to yield yellowish liquid. Yield, 6 g (40% ).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[CH2:13][CH2:12][CH2:11][O:10][C:9]2=[O:14])=[CH:4][CH:3]=1.[BrH:22]>C(O)(=O)C>[Br:22][CH2:11][CH2:12][CH2:13][C:8]([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[C:9]([OH:10])=[O:14]
Reactant: Br
Reactant: O=C1OCCCC1(c1ccc(F)cc1)c1ccc(F)cc1
Solvent: CC(=O)O
Product: O=C(O)C(CCCBr)(c1ccc(F)cc1)c1ccc(F)cc1
Temperature: 25 °C

Procedure:
A mixture of 5.8 parts of 3,3-bis(4-fluorophenyl)tetrahydro-2H-pyran-2-one and 30 parts of a solution of hydrobromic acid in glacial acetic acid was stirred over week-end at room temperature. The reaction mixture was poured onto water. The precipitated product was filtered off and dissolved in 2,2'-oxybispropane. The organic phase was washed with water, dried, filtered and evaporated. The residue was boiled in a mixture of 42 parts of 2,2'-oxybispropane and 42 parts of petroleumether. The product was filtered off and crystallized from 2,2'-oxybispropane, yielding 1.27 parts of α-(3-bromopropyl)-4-fluoro-α-(4-fluorophenyl)benzeneacetic acid; mp. 161° C. (intermediate 16).
Reaction SMILES: [F:1][B-:2]([F:5])([F:4])[F:3].[CH3:6][N:7](C)[C:8](=[S:12])[N:9]([CH3:11])[CH3:10].[CH3:14][N:15](C)[C:16](=[S:20])[N:17]([CH3:19])[CH3:18].[CH3:22][N:23](C)C(=S)N(C)C.[H+].[B-](F)(F)(F)F>O.[Au+]>[F:1][B-:2]([F:5])([F:4])[F:3].[CH3:14][N+:15]1[N:7]=[C:8]([S-:12])[N:9]([CH3:11])[C:10]=1[CH3:22].[CH3:22][N+:23]1[N:15]=[C:16]([S-:20])[N:17]([CH3:19])[C:18]=1[CH3:6]
Reactant: CN(C)C(=S)N(C)C
Agent: [Au+]
Agent: F[B-](F)(F)F
Agent: [H+]
Solvent: O
Product: Cc1n(C)c([S-])n[n+]1C
Temperature: 60 °C
Yield: 86 %

Procedure:
First the gold(I) starting compound, aurous bis(tetramethyl-thiourea) tetrafluoroborate, was made as follows. HAuCl4.3H2O (0.255 g) was dissolved in 5 mL water and added dropwise to tetramethylthiourea (0.327 g) which was partly dissolved in water. Dark orange and red precipitates formed initially, but after stirring at about 50° to 60° C. the precipitates dissolved and the solution became completely clear and colorless. 0.2 mL HBF4 solution (49% aqueous) was added. After cooling a few hours, white platelets of the product were filtered (84% yield). This intermediate gold(I) compound (0.228 g) was dissolved in 4 mL water by heating to about 60° C., and then added to a room temperature solution of 1,4,5-trimethyl-1,2,4-triazolium-3-thiolate (0.126 g). A white precipitate began to form, and was filtered after standing in the refrigerator a few hours. The product yield was 86%. The product could be recrystallized from hot water. Elemental analysis conformed to the formula for compound 1, and a single-crystal x-ray diffraction study confirmed the structure as a linear, two-coordinate complex with gold-sulfur bond lengths averaging 2.27 angstroms.
Reaction SMILES: [CH2:1]([N:8]([CH2:10][CH2:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([Cl:21])[CH:19]=2)[N:14]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH:13]=1)C)C1C=CC=CC=1.Cl[C:30]([O:32][CH3:33])=[O:31]>ClC(Cl)(Cl)C>[CH3:1][N:8]([CH2:10][CH2:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([Cl:21])[CH:19]=2)[N:14]([C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH:13]=1)[C:30]([O:32][CH3:33])=[O:31]
Reactant: CN(CCc1cn(-c2ccc(F)cc2)c2ccc(Cl)cc12)Cc1ccccc1
Reactant: COC(=O)Cl
Solvent: CC(Cl)(Cl)Cl
Product: COC(=O)N(C)CCc1cn(-c2ccc(F)cc2)c2ccc(Cl)cc12
Yield: 130 %

Procedure:
A mixture of N-benzyl-N-methyl-2-[5-chloro-1-(4-fluorophenyl)-3-1H-indolyl]ethylamine (14a) (13.7 g, 0.026 mol), methyl chloroformate (2.9 g, 0.031), K2 CO3 (4.2 g, 0.031) and 1,1,1-trichloroethane (150 mL) was heated at reflux for 2 h and the precipitates was filtered off. Evaporation of the solvents afforded crude N-methyl-N-methoxycarbonyl-2-[5-chloro-1-(4-fluorophenyl)-3-1H-indolyl]ethylamine (12.2 g) as an oil. A mixture of the crude N-methoxycarbonyl-2-[5-chloro-1-(4-fluorophenyl)-3-1H-indolyl]ethylamine (12.2 g, 0.034) and 47% hydrobromic acid (150 mL) was heated at reflux for 14 h. The reaction mixture was poured into ice, made alkaline with concentrated NaOH and extracted with diethyl ether (2×200 mL). The combined organic phases were washed with brine and dried (Na2 SO4). Evaporation of the solvents afforded pure title compound as an oil (7.9 g, 52%) which was crystalized as its maleate from ethyl acetate: mp 171°-173° C. (ethyl acetate); 1H NMR (DMSO-d6) δ 2.65 (s, 3 H), 3.05-3.20 (m, 2 H), 3.20-3.30 (m, 2 H), 6.05 (s, 2 H), 7.20 (broad d, 1 H), 7.45 (t, 2 H), 7.50 (s, 1 H), 7.60 (dd, 2 H), 7.65 (s, 1 H), 7.80 (broad s, 1 H); MS (m/z) 303 (MH+), 237 (82) 236 (100). Anal. (C17H16FClN2.C4H4O4) C, H, N.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[CH:10]([NH:18][C:19]1[CH:28]=[CH:27][CH:26]=[C:25]2[C:20]=1[CH:21]=[CH:22][C:23](=[O:29])[NH:24]2)[C:11]1([C:14]([F:17])([F:16])[F:15])[CH2:13][O:12]1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:36]([SH:38])[CH3:37].O>CN(C=O)C>[CH2:36]([S:38][CH2:13][C:11]([OH:12])([C:14]([F:16])([F:15])[F:17])[CH:10]([NH:18][C:19]1[CH:28]=[CH:27][CH:26]=[C:25]2[C:20]=1[CH:21]=[CH:22][C:23](=[O:29])[NH:24]2)[C:3]1[CH:4]=[CH:5][C:6]([O:8][CH3:9])=[CH:7][C:2]=1[F:1])[CH3:37]
Reactant: COc1ccc(C(Nc2cccc3[nH]c(=O)ccc23)C2(C(F)(F)F)CO2)c(F)c1
Reactant: CCS
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CCSCC(O)(C(Nc1cccc2[nH]c(=O)ccc12)c1ccc(OC)cc1F)C(F)(F)F
Reaction time: 4 h
Yield: 35.4 %

Procedure:
To 50 mg (0.12 mmol) 5-{[(2-Fluoro-4-methoxyphenyl)(2-trifluoromethyl-oxiranyl)methyl]amino}-1H-quinolin-2-one and 80 mg Cs2CO3 in 0.5 ml DMF are added 14 μl (0.18 mmol) of ethyl mercaptan in DMF. The mixture is stirred vigorously for 4 hours and water is added. The aqueous layer is extracted with ethyl acetate, the organic phases washed with brine and dried over sodium sulphate. After removal of the solvent thin layer chromatography on silica gel (acetone in hexane 50%) yields 20 mg of the title compound.
Reaction SMILES: [CH:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH2:8][CH2:9][C:10]2=[O:13])=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[CH3:14][CH:15](O)[CH:16]=[CH2:17].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>COC(OC)(C)C>[CH2:14]([CH:9]1[CH2:8][C:7]2[C:11](=[CH:12][C:4]([CH:1]([CH3:3])[CH3:2])=[CH:5][CH:6]=2)[C:10]1=[O:13])[CH:15]=[CH:16][CH3:17]
Reactant: C=CC(C)O
Reactant: CC(C)c1ccc2c(c1)C(=O)CC2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: COC(C)(C)OC
Solvent: O
Product: CC=CCC1Cc2ccc(C(C)C)cc2C1=O
Yield: 38 %

Procedure:
A solution of 11.2 g of 6-isopropyl-1-indanone, 13.3 ml of 3-buten-2-ol and 110 mg of p-toluenesulfonic acid in 110 ml of 2,2-dimethoxy-propane was boiled under reflux for 89 hours on a water separator filled with molecular sieve (0.4 nm, 2 mm pearl shaped). The reaction mixture was subsequently concentrated in a vacuum and purified by column chromatography on silica gel (hexane/diethyl ether 5:1). In addition to 6.6 g of educt, there were obtained 5.6 g (38%) of (RS)-2-(2-buten-1-yl)-6-isopropyl-1-indanone as a yellow oil.
Reaction SMILES: S(=O)(=O)(O)O.[C:6]1([O:12][CH2:13][CH3:14])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH2:15]([Cl:19])[C:16](=[CH2:18])[CH3:17]>>[CH2:13]([O:12][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[C:16]([CH3:18])([CH3:17])[CH2:15][Cl:19])[CH3:14]
Reactant: C=C(C)CCl
Reactant: CCOc1ccccc1
Agent: O=S(=O)(O)O
Product: CCOc1ccccc1C(C)(C)CCl
Temperature: 0 °C
Reaction time: 10 h
Yield: 213.4 %

Procedure:
120 g of 98% sulfuric acid was charged in a 500 ml four-neck flask. 200 g of phenetole was added dropwise thereto while the temperature was kept at 45° C. A mixed solution of 90 g of methallyl chloride and 165 g of phenetole was added dropwise thereto over 10 h while the temperature was kept at 0° to 10° C. The mixture was kept at 25° C. for 15 h and then poured into ice/water. An organic layer was separated out, washed thoroughly with a dilute aqueous sodium hydroxide solution and then water and dried over anhydrous sodium sulfate to obtain 451.2 g of crude 2-(2-ethoxyphenyl)-2-methylpropyl chloride. The crude product was analyzed according to gas chromatography to reveal that it comprised 22% of 2-(4-ethoxyphenyl)-2-methylpropyl chloride and 78% of 2-(2-ethoxyphenyl)-2-methylpropyl chloride (isomer).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:9]=[C:10]([O:21][CH2:22][CH2:23][O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[C:11]=1[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=1)[C:5]([O:7][CH3:8])=[O:6].[C:31]([C:35]1[CH:40]=[CH:39][C:38]([S:41](Cl)(=[O:43])=[O:42])=[CH:37][CH:36]=1)([CH3:34])([CH3:33])[CH3:32]>N1C=CC=CC=1.C1(C)C=CC=CC=1>[C:31]([C:35]1[CH:40]=[CH:39][C:38]([S:41]([NH:1][C:2]2[CH:3]=[C:4]([CH:9]=[C:10]([O:21][CH2:22][CH2:23][O:24][CH:25]3[CH2:30][CH2:29][CH2:28][CH2:27][O:26]3)[C:11]=2[O:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=2)[C:5]([O:7][CH3:8])=[O:6])(=[O:43])=[O:42])=[CH:37][CH:36]=1)([CH3:34])([CH3:32])[CH3:33]
Reactant: CC(C)(C)c1ccc(S(=O)(=O)Cl)cc1
Reactant: COC(=O)c1cc(N)c(Oc2cccc(OC)c2)c(OCCOC2CCCCO2)c1
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: COC(=O)c1cc(NS(=O)(=O)c2ccc(C(C)(C)C)cc2)c(Oc2cccc(OC)c2)c(OCCOC2CCCCO2)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
0.35 g of methyl 3-amino-4-(3-methoxy-phenoxy)-5-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-benzoate was dissolved in pyridine (10 ml), treated dropwise while cooling with ice with a solution of 0.312 g of 4-tert.butyl-benzenesulphonyl chloride in toluene (3 ml) and subsequently stirred at RT for 24 hours. The reaction mixture was poured on to ice/3M HCl, the product was extracted with ethyl acetate, the organic phase was washed with 2M KHCO3 solution and dried over magnesium sulphate. After removing the solvent there was obtained the desired methyl 3-(4-tert-butyl-benzenesulphonylamino)-4-(3-methoxy-phenoxy)-5-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-benzoate as a solid.