Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(NC(C)C)(C)C.[Li]CCCC.[CH3:13][N:14]1[CH:19]([CH3:20])[C:18]2([CH3:24])[CH:21]([CH3:23])[CH2:22][CH:15]1[CH:16]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:17]2.Cl[C:31]([O:33][CH2:34][CH3:35])=[O:32]>C1COCC1.[Cl-].[NH4+]>[CH3:13][N:14]1[CH:19]([CH3:20])[C:18]2([CH3:24])[CH:21]([CH3:23])[CH2:22][CH:15]1[C:16]([C:31]([O:33][CH2:34][CH3:35])=[O:32])([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH2:17]2
Reactant: CCOC(=O)C1CC2(C)C(C)CC1N(C)C2C
Reactant: CCOC(=O)Cl
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: CCOC(=O)C1(C(=O)OCC)CC2(C)C(C)CC1N(C)C2C
Temperature: 0 °C
Reaction time: 1 h
Yield: 62.6 %

Procedure:
To a solution of diisopropylamine (3.0 mL, 22 mmol) in THF (34 mL) at 0° C. under nitrogen was added n-BuLi (8.8 mL, 22 mmol, 2.5M in hexanes). A solution of ethyl 2,3,4,8-tetramethyl-2-azabicyclo[2.2.2]octane-6-carboxylate (4.8 g, 20 mmol) in THF (46 mL) was added to the mixture and the reaction was stirred at 0° C. for 1 hour. Ethyl chloroformate (2.3 mL, 24 mmol) in THF (3 mL) was then added and the mixture was stirred for 15 minutes. The reaction mixture was diluted with saturated ammonium chloride and partitioned between water and ether. The aqueous layer was extracted with ether (2X) and the combined organic layers were dried over anhydrous MgSO4. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel eluting with ether/hexane (15/85) to afford 3.9 g (63%) of diethyl 2,3,4,8-tetramethyl-2-azabicyclo-[2.2.2]octane-6,6-dicarboxylate as a yellow oil.
Reaction SMILES: [OH:1][C:2]1C(C(O)=O)=CC([N+]([O-])=O)=CN=1.Cl[C:15]1[C:20]([C:21](Cl)=[O:22])=[CH:19][C:18]([N+:24]([O-:26])=[O:25])=[CH:17][N:16]=1.[CH3:27][OH:28]>>[CH3:2][O:1][C:15]1[C:20]([C:21]([O:28][CH3:27])=[O:22])=[CH:19][C:18]([N+:24]([O-:26])=[O:25])=[CH:17][N:16]=1
Reactant: O=C(Cl)c1cc([N+](=O)[O-])cnc1Cl
Reactant: CO
Reactant: O=C(O)c1cc([N+](=O)[O-])cnc1O
Product: COC(=O)c1cc([N+](=O)[O-])cnc1OC

Procedure:
2-Hydroxy-3-carboxy-5-nitropyridine was converted to 2-chloro-3-chlorocarbonyl-5-nitropyridine in situ and converted to the title compound by reaction with anhydrous methanol according to the procedure of A. Monge et al J. Het. Chem. (29), 1545 (1992). In a 500 mL was added starting material (10.2 g, 54 mmol) in 200 mL of chlorobenzene. Phosphorous oxychloride (20 g, 131 mmol) was added and heated to reflux for 2 hours. The solvent was removed under reduced pressure and residual POCl3 was azeotroped off with 2×50 mL of toluene. Methanol (20 mL) was added to the mixture and the solution stirred at 25° C. for 1 hour, then refluxed overnight. Within 1 hour, all of the intermediate went into solution. There was considerable evolution of HCl. The methanol was stripped and the product neutralized with aqueous saturated sodium bicarbonate. The mixture was extracted with methylene chloride, the organic layer dried over MgSO4, filtered and the solvent removed under reduced pressure. Recovered 5.3 g of crude product. Two spots were observed by TLC (90/10 hexane/ethyl acetate); the higher Rf material (1.6 g) was 2-chloro-3-carbomethoxy-5-nitropyridine, the lower Rf product was the desired 2-methoxy-3-carbomethoxy-5-nitropyridine 850 mg (9% yield).
Reaction SMILES: [CH3:1][N:2]1[C:6]([N:7]([C:15]([O:17]CC(Cl)(Cl)Cl)=O)C(OC(Cl)(Cl)Cl)=O)=[CH:5][CH:4]=[N:3]1.[F:23][C:24]1[CH:25]=[C:26]([C:30]2[N:31]=[C:32]([N:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]3)[S:33][CH:34]=2)[CH:27]=[CH:28][CH:29]=1.C(N(C(C)C)CC)(C)C.O>CS(C)=O>[F:23][C:24]1[CH:25]=[C:26]([C:30]2[N:31]=[C:32]([N:35]3[CH2:36][CH2:37][N:38]([C:15]([NH:7][C:6]4[N:2]([CH3:1])[N:3]=[CH:4][CH:5]=4)=[O:17])[CH2:39][CH2:40]3)[S:33][CH:34]=2)[CH:27]=[CH:28][CH:29]=1
Reactant: Cn1nccc1N(C(=O)OCC(Cl)(Cl)Cl)C(=O)OC(Cl)(Cl)Cl
Reactant: Fc1cccc(-c2csc(N3CCNCC3)n2)c1
Solvent: CS(C)=O
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: Cn1nccc1NC(=O)N1CCN(c2nc(-c3cccc(F)c3)cs2)CC1
Temperature: 70 °C
Reaction time: 16 h
Yield: 58.6 %

Procedure:
A mixture of trichloromethyl 2,2,2-trichloroethyl (1-methyl-1H-pyrazol-5-yl)imidodicarbonate (255 mg, 0.570 mmol), 4-[4-(3-fluorophenyl)-1,3-thiazol-2-yl]piperazine (300 mg, 1.14 mmol) and diisopropylethylamine (0.198 ml, 1.14 mmol) in dimethyl sulfoxide (3.8 ml) was stirred at 70° C. for 16 hours. Water was poured to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate), and recrystallized from a mixed solvent of hexane and tetrahydrofuran to give 129 mg (58.8%) of the desired product as a solid.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:8]=[C:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:10]=[CH:11][C:12]=2[OH:13])=[CH:3][N:2]=1.[Cl:20][C:21]1[CH:22]=[C:23]([S:28]([N:31](CC2C=CC(OC)=CC=2OC)[C:32]2[S:33][CH:34]=[N:35][N:36]=2)(=[O:30])=[O:29])[CH:24]=[CH:25][C:26]=1F.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[Cl:20][C:21]1[CH:22]=[C:23]([S:28]([NH:31][C:32]2[S:33][CH:34]=[N:35][N:36]=2)(=[O:29])=[O:30])[CH:24]=[CH:25][C:26]=1[O:13][C:12]1[CH:11]=[CH:10][C:9]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][C:7]=1[C:4]1[CH:5]=[CH:6][N:1]=[N:2][CH:3]=1
Reactant: COc1ccc(CN(c2nncs2)S(=O)(=O)c2ccc(F)c(Cl)c2)c(OC)c1
Reactant: Oc1ccc(-c2ccccc2)cc1-c1ccnnc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: O=S(=O)(Nc1nncs1)c1ccc(Oc2ccc(-c3ccccc3)cc2-c2ccnnc2)c(Cl)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 49.1 %

Procedure:
3-Pyridazin-4-ylbiphenyl-4-ol (Preparation 4, 40 mg, 0.16 mmol) and 3-chloro-N-(2,4-dimethoxybenzyl)-4-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 17, 72 mg, 0.16 mmol) were dissolved in dimethylsulfoxide (2 mL). Potassium carbonate (67 mg, 0.5 mmol) was added and the reaction stirred at room temperature for 16 hours. The crude material was partitioned between ethyl acetate (20 mL) and water (20 mL), the organic layer separated, concentrated in vacuo, dissolved in trifluoroacetic acid (1 mL) and the solution stirred for 16 hours at room temperature. The reaction was then concentrated in vacuo and purified by silica gel column chromatography (ISCO™, 12 g silica, 50-100% ethyl acetate in heptane gradient elution). The appropriate fractions were combined and concentrated in vacuo to afford the title compound as a white solid (41 mg, 49%).
Reaction SMILES: [C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:23]=[CH:22][C:17]([C:18]([O:20]C)=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][N:26]=2)[CH2:6][C@@H:5]1[CH3:33])(=[O:3])[CH3:2].[OH-].[Na+].C(O)(=O)C>CO>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[CH:16][C:17]([C:18]([OH:20])=[O:19])=[CH:22][CH:23]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][N:26]=2)[CH2:6][C@@H:5]1[CH3:33])(=[O:3])[CH3:2]
Reactant: COC(=O)c1ccc(-c2ccc3c(c2)[C@H](Nc2ccc(C#N)cn2)C[C@H](C)N3C(C)=O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CO
Product: CC(=O)N1c2ccc(-c3ccc(C(=O)O)cc3)cc2[C@H](Nc2ccc(C#N)cn2)C[C@@H]1C
Reaction time: 24 h
Yield: 85 %

Procedure:
A solution of methyl 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoate (for a preparation see Intermediate 3) (1.0 g, 2.270 mmol) in MeOH (15 mL) at room temperature was treated with aqueous sodium hydroxide solution (2N, 2.27 mL, 4.54 mmol) and the resulting mixture was stirred at this temperature for 24 h. The bulk of MeOH was evaporated in vacuo and the aqueous residue was treated with acetic acid (0.39 mL, 6.81 mmol) giving precipitate which was isolated by filtration and dried under vacuum at 40° C. to afford 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid (820 mg, 1.923 mmol, 85% yield) as a yellow solid. LCMS (HpH, 2 min), Rt=0.64 min, MH+=427.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([O:13][CH3:14])[C:10]=1[O:11][CH3:12])[CH:6]=[O:7].[N+:15]([CH:18](O)[CH3:19])([O-:17])=[O:16].C(Cl)(Cl)Cl.C(O)(=[O:27])C>CO.CN1CCCCC1>[CH3:14][O:13][C:9]1[CH:8]=[C:5]([CH:6]([OH:7])[CH:18]([N+:15]([O-:17])=[O:16])[CH2:19][OH:27])[CH:4]=[C:3]([O:2][CH3:1])[C:10]=1[O:11][CH3:12]
Reactant: CC(O)[N+](=O)[O-]
Reactant: COc1cc(C=O)cc(OC)c1OC
Reactant: CC(=O)O
Solvent: ClC(Cl)Cl
Solvent: CN1CCCCC1
Solvent: CO
Product: COc1cc(C(O)C(CO)[N+](=O)[O-])cc(OC)c1OC
Temperature: 0 °C
Reaction time: 6 h

Procedure:
19.6 g (0.1 moles) of 3,4,5-trimethoxybenzaldehyde and 9.1 g (0.1 moles) of nitroethanol are suspended in a mixture of 25 ml of methanol and 1 ml of N-methylpiperidine at a temperature of 0° C. (under cooling with ice water). The reaction mixture is stirred for 6 hours, then 50 ml of chloroform are added, the mixture is allowed to stand at 0° C. for 72 hours and then acidified with 1 ml of acetic acid. The separated crystalline substance is filtered off, washed with chloroform and ice-cold (0° C.) water and dried. 19.7 g 68.64%) of 1-(3,4,5-trimethoxyphenyl)-2-nitro-1,3-propanediol are obtained; m.p.: 155°-159° C.
Reaction SMILES: [CH3:1][N:2]1[C:6]([OH:7])=[CH:5][C:4]([C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10])=[N:3]1.Cl[C:16]1[N:17]=[N:18][CH:19]=[C:20]([O:22][CH3:23])[CH:21]=1.N1C(C)=CC=CC=1C.C(OCC)(=O)C>C1(C)C=CC=CC=1>[CH3:23][O:22][C:20]1[CH:21]=[C:16]([O:7][C:6]2[N:2]([CH3:1])[N:3]=[C:4]([C:8]([F:13])([F:14])[C:9]([F:11])([F:10])[F:12])[CH:5]=2)[N:17]=[N:18][CH:19]=1
Reactant: Cn1nc(C(F)(F)C(F)(F)F)cc1O
Reactant: COc1cnnc(Cl)c1
Solvent: Cc1cccc(C)n1
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: COc1cnnc(Oc2cc(C(F)(F)C(F)(F)F)nn2C)c1

Procedure:
1-Methyl-3-(pentafluoroethyl)-1H-pyrazol-5-ol (0.44 g, 0.002 mole), 3-chloro-5-methoxypyridazine (0.29 g, 0.002 mole), and 2,6-lutidine (0.27 g, 0.0024 mole) were refluxed under N2 in toluene (8 mL) for 15 h. This mixture was poured into ethyl acetate and washed with 7% HCl, water and then with saturated sodium bicarbonate. The organic layer was dried (MgSO4), filtered through silica gel with ethyl acetate, and evaporated in vacuo to give 5-methoxy-3-[[1-methyl-3-(pentafluoroethyl)-1H-pyrazol-5-yl]oxy]pyridazine as a light yellow solid. The compound was recrystallized to give (0.45 g, 69% yield) Compound 18, a white solid.
Reaction SMILES: [C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]#[N:14])=[CH:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:15]([NH:23][NH2:24])(=O)[C:16]1[CH:21]=[CH:20][CH:19]=[N:18][CH:17]=1>CC1C=CC=CC=1C.ClCCl.CO>[C:1]1([C:7]2[N:12]=[CH:11][C:10]([C:13]3[N:14]=[C:15]([C:16]4[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=4)[NH:23][N:24]=3)=[CH:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: N#Cc1cnc(-c2ccccc2)nc1
Reactant: NNC(=O)c1cccnc1
Solvent: CO
Solvent: Cc1ccccc1C
Solvent: ClCCl
Product: c1ccc(-c2ncc(-c3n[nH]c(-c4cccnc4)n3)cn2)cc1
Yield: 9.7 %

Procedure:
2-Phenyl-pyrimidine-5-carbonitrile (Biofine International, 0.20 g, 1.10 mmol) and nicotinic hydrazide (Aldrich, 0.151 g, 1.10 mmol) were dissolved in o-xylene (5 mL) and heated to 200° C. under nitrogen atmosphere for seven hours as the o-xylene slowly boiled off. The remaining crude solid was dissolved in a minimal amount of 98:2 v/v dichloromethane-methanol and purified by flash silica column chromatography. Elution through a 40-g Analogix® flash silica cartridge with 100% dichloromethane to 5% methanol in dichloromethane afforded the title compound as a yellow solid (32 mg, 10% yield); Rf 0.27 with 95:5 v/v dichloromethane-methanol; melting point 322-333° C.; 1H-NMR (400 MHz; CDCl3) δ 9.53 (s, 2H), 9.32 (d, 1H), 8.76-8.75 (m, 1H), 8.53-8.46 (m, 3H), 7.64-7.60 (m, 4H); MS (ESI+) m/z 301.1 (M+1); H-PGDS FPBA IC50: 1 μM.
Reaction SMILES: Cl.[NH2:2][C@@H:3]([C:9]([CH3:12])([CH3:11])[CH3:10])[C:4]([N:6]([CH3:8])[CH3:7])=[O:5].[CH2:13]([O:20][C:21](=[O:31])[C@@H:22]([O:27][C:28](Cl)=[O:29])[CH2:23][CH:24]([CH3:26])[CH3:25])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C(OCC)(=O)C>[CH2:13]([O:20][C:21](=[O:31])[C@@H:22]([O:27][C:28](=[O:29])[NH:2][C@H:3]([C:4](=[O:5])[N:6]([CH3:8])[CH3:7])[C:9]([CH3:12])([CH3:11])[CH3:10])[CH2:23][CH:24]([CH3:25])[CH3:26])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CC(C)C[C@H](OC(=O)Cl)C(=O)OCc1ccccc1
Reactant: CN(C)C(=O)[C@@H](N)C(C)(C)C
Agent: Cl
Solvent: CCOC(C)=O
Product: CC(C)C[C@H](OC(=O)N[C@H](C(=O)N(C)C)C(C)(C)C)C(=O)OCc1ccccc1
Yield: 85.6 %

Procedure:
(2S)-2-Amino-3,3-dimethyl-N,N-dimethylbutyramide hydrochloride (0.25 g), (2S)-2-chlorocarbonyloxy-4-methylvaleric acid benzylester (0.36 g) and TEA (0.31 g) were reacted in ethyl acetate (10 ml) in a similar manner to that of Example 4-1) to give (2S)-2-[N-[(1S)-2,2-dimethyl-1-(N,N-dimethylcarbamoyl)propyl]carbamoyloxy]-4-methylvaleric acid benzyl ester (0.44 g).
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([CH3:9])=[CH:7][N:6]=[C:5]([CH2:10]O)[C:4]=1[CH3:12].S(Cl)([Cl:15])=O.CCOCC>C(Cl)Cl>[ClH:15].[Cl:15][CH2:10][C:5]1[C:4]([CH3:12])=[C:3]([O:2][CH3:1])[C:8]([CH3:9])=[CH:7][N:6]=1
Reactant: O=S(Cl)Cl
Reactant: COc1c(C)cnc(CO)c1C
Solvent: ClCCl
Solvent: CCOCC
Product: COc1c(C)cnc(CCl)c1C
Product: Cl
Temperature: 25 °C
Reaction time: 2 h

Procedure:
75.8 g of 4-methoxy-3,5-dimethyl-2-pyridylmethanol, dissolved in 200 ml of methylene chloride, were added dropwise at 0° to 38 ml of thionyl chloride in 400 ml of methylene chloride. After stirring at room temperature for 16 hours 1800 ml of ether were added dropwise thereto while cooling and the mixture was stirred at room temperature for a further 2 hours. The precipitated crystals were filtered off under suction and washed with ether. There was obtained 2-(chloromethyl)-4-methoxy-3,5-dimethylpyridine hydrochloride of melting point 130°-131°.
Reaction SMILES: [C:1](=[S:3])=S.[OH-].[K+].[N+:6]([C:9]1[CH:10]=[C:11](O)[C:12]([OH:15])=[CH:13][CH:14]=1)([O-])=O.S(S([O-])=O)([O-])=[O:18].[Na+].[Na+]>O.CO>[OH:15][C:12]1[CH:11]=[CH:10][C:9]2[N:6]=[C:1]([SH:3])[O:18][C:14]=2[CH:13]=1
Reactant: O=S([O-])S(=O)[O-]
Reactant: S=C=S
Reactant: O=[N+]([O-])c1ccc(O)c(O)c1
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: Oc1ccc2nc(S)oc2c1
Temperature: 75 °C
Reaction time: 0.17 h

Procedure:
Carbon disulphide (0.9 ml, 15 mmol) was added to a solution of potassium hydroxide (0.65 g, 11 mmol) in a mixture of water (1 ml) and methanol (10 ml), followed by 4-nitro 1,2-benzenediol (1.5 g, 10 mmol). To this mixture was added dropwise a solution of sodium dithionite (6,5 g, 30 mmol) and potassium hydroxide (3.9 g, 70 mmol) in water (50 ml); strong heat evolution was observed. After 10 minutes, carbon disulphide (0.9 ml, 15 mmol) was added and the mixture heated to 75° C. for 3 hours. The mixture was then cooled in an ice bath and the precipitate filtered off. The filtrate was acidified to approximately pH3 with concentrated hydrochloric acid and the yellow precipitate was collected, washed with water and air dried. The yield was 1.05 g (65%).
Reaction SMILES: [SH:1][C:2]1[S:3][CH:4]=[CH:5][CH:6]=1.C(N(CC)CC)C.[CH3:14][C@H:15]1[O:19][C:17](=[O:18])[CH2:16]1>O1CCCC1>[S:3]1[CH:4]=[CH:5][CH:6]=[C:2]1[S:1][C@@H:15]([CH3:14])[CH2:16][C:17]([OH:19])=[O:18]
Reactant: C[C@@H]1CC(=O)O1
Reactant: Sc1cccs1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C[C@@H](CC(=O)O)Sc1cccs1
Reaction time: 0.17 h
Yield: 93.5 %

Procedure:
To a magnetically-stirred 25 mL round-bottomed flask blanketed with nitrogen was charged 2-mercaptothiophene (0.73 g, 6.29 mmol) in tetrahydrofuran (7 mL, K.F. <0.1 mg/mL) at 25° C. Triethylamine (0.87 mL, 6.29 mmol) was injected and the reaction mixture was stirred for 10 minutes to complete salt formation. To this mixture was added (R)-(+)-β-methyl-β-propiolactone (0.54 g, 6.29 mmol) in one portion and the reaction mixture was stirred at 25° C. for approximately 3 hours. When complete, the mixture was stripped of solvent on a rotary evaporator at 25° C. and diluted with ethyl acetate (10 mL) and water (10 mL). The pH of the mixture was then adjusted to 2.0 with 5N hydrochloric acid and the layers separated. The upper ethyl acetate product layer was dried over sodium sulfate and concentrated to an oil on a rotary evaporator. Silica gel chromatography (10% ethyl acetate/hexanes) afforded 1.19 g of (S)-3-(2-thienylthio)butyric acid (94%).
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[C:12]2[C:13]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20][C:14]=3[NH:15][C:16]=2[CH:17]=[CH:18][CH:19]=1)[CH2:2][CH3:3].I[CH2:26][CH2:27]C>>[CH2:1]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[C:12]2[C:13]3[CH2:24][CH2:23][NH:22][CH2:21][CH2:20][C:14]=3[NH:15][C:16]=2[CH:17]=[CH:18][CH:19]=1)[CH2:2][CH2:3][CH2:26][CH3:27]
Reactant: CCCOc1ccccc1-c1cccc2[nH]c3c(c12)CCNCC3
Reactant: CCCI
Product: CCCCCOc1ccccc1-c1cccc2[nH]c3c(c12)CCNCC3

Procedure:
Following the procedure for the preparation of 10-(2-propoxyphenyl)-1,2,3,4,5,6-hexahydroazepino[4,5-b]indole and substituting 1-iodopentane for 1-iodopropane while making non-critical variations the title compound was obtained as 361 mg (71%) of a brown oil: 1H NMR (400 MHz, CDCl3) δ 7.83 (br s, 1H), 7.36-7.28 (m, 3 H), 7.17-7.13 (m, 1H), 7.05-7.01 (m, 1H), 6.97 (d, J=8.2 Hz, 1H), 6.93 (d, J=7.2 Hz, 1H), 3.95-3.85 (m, 2H), 3.12-3.10 (m, 1H), 3.06-3.04 (m, 1H), 2.98-2.93 (m, 2H), 2.88-2.85 (m, 1H), 2.81-2.79 (m, 1H), 2.42-2.37 (m, 2H), 1.59-1.52 (m, 2H), 1.21-1.13 (m, 4 H), 0.79 (t, J=7.0 Hz, 3 H); HRMS (FAB) calcd for C23H28N2O+H1: 349.2280 found 349.2280.
Reaction SMILES: [F:1][C:2]1[CH:22]=[CH:21][CH:20]=[C:19]([F:23])[C:3]=1[CH2:4][O:5][C:6]1[N:11]2[N:12]=[C:13]([CH3:18])[C:14]([C:15]([OH:17])=O)=[C:10]2[CH:9]=[CH:8][CH:7]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[C:46]([O:50][C:51](=[O:60])[NH:52][C:53]([CH3:59])([CH2:56][CH2:57][CH3:58])[CH2:54][NH2:55])([CH3:49])([CH3:48])[CH3:47].C(N(CC)C(C)C)(C)C>O1CCCC1>[C:46]([O:50][C:51](=[O:60])[NH:52][C:53]([CH3:59])([CH2:56][CH2:57][CH3:58])[CH2:54][NH:55][C:15]([C:14]1[C:13]([CH3:18])=[N:12][N:11]2[C:6]([O:5][CH2:4][C:3]3[C:2]([F:1])=[CH:22][CH:21]=[CH:20][C:19]=3[F:23])=[CH:7][CH:8]=[CH:9][C:10]=12)=[O:17])([CH3:49])([CH3:48])[CH3:47]
Reactant: Cc1nn2c(OCc3c(F)cccc3F)cccc2c1C(=O)O
Reactant: CCCC(C)(CN)NC(=O)OC(C)(C)C
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CCCC(C)(CNC(=O)c1c(C)nn2c(OCc3c(F)cccc3F)cccc12)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
A solution of 100 mg (0.19 mmol, 61% pure) of 7-[(2,6-difluorobenzyl)oxy]-2-methylpyrazolo[1,5-a]pyridine-3-carboxylic acid from Example 130A in 4 ml of tetrahydrofuran was admixed with 39.1 mg (0.287 mmol) of 1-hydroxybenzotriazole and 74.3 mg (0.287 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The resulting solution was stirred at room temperature for 15 min, and then 62.2 mg (0.287 mmol) of rac-(1-amino-2-methylpentan-2-yl)carbamic acid tert-butyl ester from Example 152A were added, followed by 0.1 ml (0.575 mmol) of N,N-diisopropylethylamine After the addition, the mixture was stirred at room temperature for a further 15 h. The solvent was drawn off under reduced pressure and the residue was partitioned between dichloromethane (10 ml) and water (10 ml). The organic phase was removed and washed with water and saturated aqueous sodium chloride solution, dried with a phase separation cartridge and concentrated under reduced pressure, which gave 45 mg (24% of theory, 53% pure) of the target compound.
Reaction SMILES: S([O-])([O-])=[O:2].[Ca+2:5].S(=O)=O.[S:9](=[O:13])(=[O:12])([OH:11])[OH:10]>>[OH2:2].[S:9]([O-:13])([O-:12])(=[O:11])=[O:10].[Ca+2:5].[Ca+2:5].[S:9]([O-:13])([O-:12])(=[O:11])=[O:10]
Reactant: O=S([O-])[O-]
Reactant: O=S(=O)(O)O
Agent: O=S=O
Agent: [Ca+2]
Product: O
Product: O=S(=O)([O-])[O-]

Procedure:
A process for producing hydrogen and/or hemihydrate calcium sulphate from calcium sulphite. Waste solid containing calcium sulphite and other calcium salts is treated by the addition of aqueous sulphur dioxide solution or sulphuric acid solution to produce a liquid phase product. The liquid phase product may be separated from any remaining solid phase material and then subjected to the addition of sulphuric acid in a second step, wherein calcium sulphate hemihydrate is produced. The addition of sulphuric acid to the liquid phase results in the evolution of sulphur dioxide which may be used as such or in sulphur dioxide electrolysis cells in order to produce hydrogen and sulphuric acid. An especially unique feature of the process is that the sulphuric acid produced in generating hydrogen can be recycled to the step where the calcium sulphate crystals are produced.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH3:12][C:13]1[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][S:27][C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH2:35][C:36]3[CH:45]=[CH:44][C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[N:37]=3)[CH:29]=2)[C:14]=1[C:15]([O:17][CH2:18][CH:19]([CH3:21])[CH3:20])=[O:16]>ClCCl>[CH3:12][C:13]1[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][S:27]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH2:35][C:36]3[CH:45]=[CH:44][C:43]4[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=4)[N:37]=3)[CH:29]=2)=[O:9])[C:14]=1[C:15]([O:17][CH2:18][CH:19]([CH3:21])[CH3:20])=[O:16]
Reactant: Cc1cccc(CSc2cccc(OCc3ccc4ccccc4n3)c2)c1C(=O)OCC(C)C
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: Cc1cccc(CS(=O)c2cccc(OCc3ccc4ccccc4n3)c2)c1C(=O)OCC(C)C
Reaction time: 8 h

Procedure:
m-Chloroperbenzoic acid (<86%, 34 mg, 0.17 mmol) is added to a solution of isobutyl 2-methyl-6-[3-(quinolin-2-ylmethoxy)-phenylsulfanylmethyl]-benzoate (80 mg, 0.17 mmol, example 84) in dichloromethane (1 mL) and the reaction is stirred overnight. The reaction is partitioned between ethyl acetate and sodium bicarbonate and the organic phase is washed with additional bicarbonate solution, dried over magnesium sulfate, concentrated and purified by column chromatography (silica, 40% ethyl acetate in hexanes) to provide the title compound. MS (ESD) 488 (M+H)+.