Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:21]3[C:20]4[CH:19]=[C:18]([O:22][CH:23]([C:27]5[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=5)[C:24](O)=[O:25])[C:17]([O:34][CH3:35])=[CH:16][C:15]=4[N:14]=[CH:13][C:12]=3[N:11]([CH3:36])[N:10]=2)=[CH:5][CH:4]=1)#[N:2].C1(C)C=CC=CC=1.S(Cl)([Cl:46])=O>>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:21]3[C:20]4[CH:19]=[C:18]([O:22][CH:23]([C:27]5[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=5)[C:24]([Cl:46])=[O:25])[C:17]([O:34][CH3:35])=[CH:16][C:15]=4[N:14]=[CH:13][C:12]=3[N:11]([CH3:36])[N:10]=2)=[CH:5][CH:4]=1)#[N:2]
Reactant: COc1cc2ncc3c(c(-c4ccc(C#N)cc4)nn3C)c2cc1OC(C(=O)O)c1ccc(F)cc1
Reactant: O=S(Cl)Cl
Solvent: Cc1ccccc1
Product: COc1cc2ncc3c(c(-c4ccc(C#N)cc4)nn3C)c2cc1OC(C(=O)Cl)c1ccc(F)cc1

Procedure:
[1-(4-Cyanophenyl)-7-methoxy-3-methyl-3H-pyrazolo[3,4-c]quinolin-8-yloxy]-(4-fluorophenyl)acetic acid (190 mg, 394 μmol) is dissolved in thionyl chloride (2.0 ml) and heated under reflux for 2 h. The mixture is then evaporated to dryness in vacuo and co-evaporated twice with distilled, anhydrous toluene, giving [1-(4-cyanophenyl)-7-methoxy-3-methyl-3H-pyrazolo[3,4-c]quinolin-8-yloxy]-(4-fluorophenyl)acetyl chloride (195 mg, 389 μmol). 35 mg (69.9 μmol) of the acid chloride obtained are subsequently dissolved in anhydrous N,N-dimethylformamide (2.0 ml) in a dry nitrogen atmosphere, and 2-(4-ethylpiperazin-1-yl)-ethylamine (22 mg, 140 μmol) is added with ice-bath cooling. The reaction solution is stirred at room temperature for 2 h. The mixture is then poured into water (30 ml) and extracted four times with ethyl acetate (30 ml each time). The combined organic phases are washed twice with water (20 ml each time), subsequently dried using Na2SO4, filtered with suction, and the filtrate is evaporated to dryness in vacuo. The residue is dissolved in dimethyl sulfoxide and chromatographed (pHPLC, solvent gradient water/1-30% by vol. of acetonitrile, 0.1% by vol. of formic acid), giving, after freeze-drying, the title compound 2-[1-(4-cyanophenyl)-7-methoxy-3-methyl-3H-pyrazolo[3,4-c]quinolin-8-yloxy]-N-[2-(4-ethylpiperazin-1-yl)ethyl]-2-(4-fluorophenyl)acetamide (21 mg, 33.8 μmol) as lyophilisate having a melting range of 110-112° C. MS: 622.3 (M+H+), TLC (HPTLC): Rf=0.40 (methanol/Hünig's base 99:1, parts by volume).
Reaction SMILES: C([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])C>C1COCC1.CCO.[OH-].[Na+]>[C:9]1([C@H:7]2[CH2:8][C@@H:6]2[C:4]([OH:5])=[O:3])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CCOC(=O)[C@H]1C[C@@H]1c1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: O=C(O)[C@H]1C[C@@H]1c1ccccc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of (1S,2S)-2-phenyl-cyclopropanecarboxylic acid ethyl ester (42 mg, 0.22 mmol, 1.0 eq.) in THF (0.68 mL) and EtOH (0.18 mL), 1M aq. NaOH (0.32 ml) was added. The solution was stirred at r.t. for 18 hours. The organic solvents were removed in vacuo. The residue was diluted with water and washed with AcOEt. The aq. phase was acidified with 2N aq. HCl soln. The mixture was extracted with DCM (3×). The comb. org. phases were dried over MgSO4, filtered and concentrated in vacuo to give the title compound as a colorless oil. The product was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][N:8]=[C:7]([O:10][CH2:11][CH:12]([NH:19]C(OC(C)(C)C)=O)[CH2:13][O:14][C:15](=[S:18])[NH:16][CH3:17])[C:6]=2[CH:27]=1.O1CCOCC1.Cl.CC(O)C>CO>[ClH:1].[NH2:19][CH:12]([CH2:13][O:14][C:15](=[S:18])[NH:16][CH3:17])[CH2:11][O:10][C:7]1[C:6]2[CH:27]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[O:9][N:8]=1
Reactant: CNC(=S)OCC(COc1noc2ccc(Cl)cc12)NC(=O)OC(C)(C)C
Agent: Cl
Solvent: CC(C)O
Solvent: C1COCCO1
Solvent: CO
Product: CNC(=S)OCC(N)COc1noc2ccc(Cl)cc12

Procedure:
To a solution of 0.4 g of 5-chloro-3-(2-tert-butoxycarbonylamino-3-methylthiocarbamoyloxypropoxy)-1,2-benzoisoxazole in 10 ml of methanol is added 5 ml of a dioxane solution (3.2N) of hydrogen chloride at room temperature, and they are subjected to reaction at the same temperature for three hours, after which the solvent is removed by distillation under reduced pressure. To the residue obtained is added 3 ml of 2-propanol, and the crystals precipitated are collected by filtration, to obtain 0.22 g of pale yellow, crystalline 3-(2-amino-3-methylthiocarbamoyloxypropoxy)-5-chloro-1,2-benzoisoxazole hydrochloride having a melting point of 198.8°-199.2° C. (decomp.).
Reaction SMILES: [C:1]1([N:7]([C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C:8]([N:10]2[CH2:15][CH2:14][C@@H:13]([C:16]([N:18]([CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])=[O:17])[CH2:12][C@@H:11]2[C:29]([NH:31][CH2:32][CH2:33][N:34](C(OCC2C=CC=CC=2)=O)[CH2:35][C:36]([NH2:38])=[O:37])=[O:30])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C(O)C.[Pd]>[C:49]1([N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]([N:10]2[CH2:15][CH2:14][C@@H:13]([C:16]([N:18]([CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[O:17])[CH2:12][C@@H:11]2[C:29]([NH:31][CH2:32][CH2:33][NH:34][CH2:35][C:36]([NH2:38])=[O:37])=[O:30])=[O:9])[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1
Reactant: CCCCCN(CCCCC)C(=O)[C@@H]1CCN(C(=O)N(c2ccccc2)c2ccccc2)[C@@H](C(=O)NCCN(CC(N)=O)C(=O)OCc2ccccc2)C1
Agent: [Pd]
Solvent: CCO
Product: CCCCCN(CCCCC)C(=O)[C@@H]1CCN(C(=O)N(c2ccccc2)c2ccccc2)[C@@H](C(=O)NCCNCC(N)=O)C1
Reaction time: 3 h
Yield: 86.9 %

Procedure:
A solution of 0.055 g (0.074 mmole) of trans 1-(N,N-diphenylaminocarbonyl)-2-(RS)-(2-(N-(benzyloxycarbonyl)-N-(aminocarbonylmethyl)amino)ethylaminocarbonyl)-4-(RS)-(N,N-dipentylaminocarbonyl)piperidine (prepared in Example 3, Step D above) in 5 mL of ethanol was treated with 32 mg of 10% palladium on carbon and the resulting slurry was then stirred under an atmosphere of hydrogen for 3 hr. The mixture was then filtered through a cake of Celite, the cake was washed with 100 mL of ethanol, and the filtrate was concentrated in vacuo, to give 39 mg (87%) of an oil.
Reaction SMILES: [C:1]([CH2:4][O:5][C:6]1[CH:11]=[C:10]([O:12][CH2:13][CH:14]=[C:15]([CH3:17])[CH3:16])[CH:9]=[CH:8][C:7]=1[C:18](=[O:20])[CH3:19])([OH:3])=[O:2].[CH2:21]([C:28]1[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=1)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27].[OH-].[K+]>C(O)C>[C:1]([CH2:4][O:5][C:6]1[CH:11]=[C:10]([O:12][CH2:13][CH:14]=[C:15]([CH3:16])[CH3:17])[CH:9]=[CH:8][C:7]=1[C:18](=[O:20])[CH:19]=[CH:32][C:31]1[CH:34]=[CH:35][C:28]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])=[CH:29][CH:30]=1)([OH:3])=[O:2]
Reactant: CCCCCCCc1ccc(C=O)cc1
Reactant: CC(=O)c1ccc(OCC=C(C)C)cc1OCC(=O)O
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: CCCCCCCc1ccc(C=CC(=O)c2ccc(OCC=C(C)C)cc2OCC(=O)O)cc1
Reaction time: 5 h

Procedure:
To a solution of 3.48 9 of 2'-carboxymethoxy-4'-(3-methyl-2-butenyloxy)acetophenone and 2.80 g of 4-n-heptylbenzaldehyde in 120 ml of ethanol was added 3.5 g of potassium hydroxide, and the mixture was stirred for 5 hours. After neutralization with dilute sulfuric acid, the resulting precipitate was collected by filtration, washed with water, dried and recrystallized from ethanol to give 4.10 g of 2'-carboxymethoxy-4-n-heptyl-4'-(3-methyl-2-butenyloxy)chalcone as pale yellow needles.
Reaction SMILES: [OH:1][C@@H:2]([C@H:4]1[C:24](=[O:25])[N:6]2[C@@H:7]([C:11]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=3)=[O:12])[C:8](=O)[CH2:9][C@H:5]12)[CH3:3].C(N(CC)C(C)C)(C)C.FC(F)(F)S(O)(=O)=O.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1.C([Sn](CCCC)(CCCC)[C:64]1[N:65]2[CH:71]=[N:70][CH:69]=[C:66]2[S:67][CH:68]=1)CCC>C(#N)C.C(OCC)(=O)C.CN1CCCC1=O.C(=O)([O-])O.[Na+].[Cl-].[Zn+2].[Cl-].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:1][C@@H:2]([C@H:4]1[C:24](=[O:25])[N:6]2[C:7]([C:11]([O:13][CH2:14][C:15]3[CH:16]=[CH:17][C:18]([N+:21]([O-:23])=[O:22])=[CH:19][CH:20]=3)=[O:12])=[C:8]([C:64]3[N:65]4[CH:71]=[N:70][CH:69]=[C:66]4[S:67][CH:68]=3)[CH2:9][C@H:5]12)[CH3:3]
Reactant: C[C@@H](O)[C@H]1C(=O)N2[C@@H](C(=O)OCc3ccc([N+](=O)[O-])cc3)C(=O)C[C@H]12
Reactant: CCCC[Sn](CCCC)(CCCC)c1csc2cncn12
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: O=C([O-])O
Solvent: CCOC(C)=O
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: C[C@@H](O)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(c3csc4cncn34)C[C@H]12
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 47.1 %

Procedure:
To an ice-cooled solution of 493 mg of 4-nitrobenzyl (3R,5R,6S)-6-((1R)-1-hydroxyethyl)-2-oxo-1-carbapenam-3-carboxylate in 13 ml of dry acetonitrile 13 ml was added dropwise 0.619 ml of N,N-diisopropylethylamine, followed by 0.235 ml of anhydrous trifluoro-methanesulfonic acid under the atmosphere of argon. After the reaction mixture was stirred at the same temperature for 30 minutes, it was diluted with ethyl acetate, and washed with semi-saturated aqueous saline, a mixed solution of semi-saturated aqueous saline and 1 N hydrochloric acid (pH 1.1), a mixed solution of semi-saturated aqueous saline and saturated aqueous sodium hydrogen carbonate (pH 8.9), and semi-saturated aqueous saline in this sequence.-The organic layer was dried over anhydrous magnesium sulfate, filtered, and the solvent was removed under reduced pressure. The residue thus obtained was dissolved in 5 ml of dry N-methylpyrrolidinone, mixed with 40 mg of tri-2-furylphosphine, 384 mg of zinc chloride, 40 mg of tris(dibenzylideneacetone)dipalladium (0), and 950 mg of 3-(tri-n-butylstannyl)imidazo[5,1-b]thiazole in 2 ml of dry N-methyl-pyrrolidinone, and the mixture was stirred under the atmosphere of argon at 50° C. for 1.5 hours. The reaction mixture was diluted with 50 ml of ethyl acetate and 50 ml of semi-saturated aqueous sodium hydrogen carbonate, the insolubles was removed by filtration, and the filtrate was washed with ethyl acetate. The organic layer of the filtrate was separated, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue thus obtained was purified by column chromatography on silica gel (chloroform:methanol=15:1) to give 303 mg of 4-nitrobenzyl (5R,6S)-6-((1R)-1-hydroxyethyl)-2-(imidazo[5,1-b]thiazol-3-yl)-1-carbapen-2-em-3-carboxylate.
Reaction SMILES: [OH-].[Na+].[OH-].[NH4+:4].[Cl-].[NH4+].[Cl:7][C:8]1[CH:12]=[CH:11][NH:10][C:9]=1[C:13]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH3:22])=[O:14].Cl[O-].[Na+]>CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].C(OCC)C.C(OC)(C)(C)C.C(OCC)(=O)C>[NH2:4][N:10]1[CH:11]=[CH:12][C:8]([Cl:7])=[C:9]1[C:13]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH3:22])=[O:14]
Reactant: Cc1ccccc1NC(=O)c1[nH]ccc1Cl
Reactant: [NH4+]
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: [Cl-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CCOC(C)=O
Solvent: COC(C)(C)C
Product: Cc1ccccc1NC(=O)c1c(Cl)ccn1N
Yield: 86 %

Procedure:
In a 100 mL three-necked flask it was placed 11 mL of a 28% aqueous solution of sodium hydroxide, 4.1 mL of a 28% ammonium hydroxide solution, 1.23 g of ammonium chloride and 0.12 mL of Aliquat 336. Afterwards, a solution of 3-chloro-N-o-tolyl-1H-pyrrole-2-carboxamide (0.9 g, 3.84 mmol) in 30 mL of diethyl ether and 30 mL of methyl tert-butyl ether was added and placed at 0° C. affording a suspension. Over this suspension, a 10% aqueous solution of sodium hypochlorite (26 mL) was added drop wise with vigorous stirring maintaining the temperature during 20 min. more. Subsequently, the reaction mixture was stirred at room temperature during a further 1.5 h producing the consumption of the starting material. Next, the reaction crude was diluted with ethyl acetate until no suspended material was observed. The layers were separated and the organic phase was washed with a 25% aqueous solution of sodium thiosulphate, water and brine, dried (Na2SO4) and concentrated under vacuum to give a residue that was triturated with hexane to produce a solid (870 mg, 86% yield) after filtration.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:22]=[CH:23][C:24]=1[O:25][CH3:26])[C:6]1[O:7][C:8]2[C:13]([C:14](=[O:16])[CH:15]=1)=[CH:12][CH:11]=[C:10]([O:17][CH2:18][CH:19]1[O:21][CH2:20]1)[CH:9]=2.[CH:27]([NH2:30])([CH3:29])[CH3:28]>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:22]=[CH:23][C:24]=1[O:25][CH3:26])[C:6]1[O:7][C:8]2[C:13]([C:14](=[O:16])[CH:15]=1)=[CH:12][CH:11]=[C:10]([O:17][CH2:18][CH:19]([OH:21])[CH2:20][NH:30][CH:27]([CH3:29])[CH3:28])[CH:9]=2
Reactant: COc1ccc(-c2cc(=O)c3ccc(OCC4CO4)cc3o2)cc1OC
Reactant: CC(C)N
Solvent: CO
Product: COc1ccc(-c2cc(=O)c3ccc(OCC(O)CNC(C)C)cc3o2)cc1OC

Procedure:
3′,4′-Dimethoxy-7-(2,3-epoxy-propoxy)-flavone, 33 (300 mg, 0.85 mmol) and iso-propyl amine (0.15 mL, 1.7 mmol) in dry methanol (80 mL) were reacted in a similar manner to that described under 34 to afford 46. Yield 290 mg (83%); mp 144-145° C.; MS (FAB) 414 (M++1); IR (KBr) 3410, 1634; 1H NMR (200 MHz, CDCl3) δ 8.03 (d, J=9.5 Hz, 1H), 7.51 (dd, J=8.5 Hz, 1.7 Hz, 1H), 7.36 (d, J=1.7 Hz, 1H), 6.96-6.92 (m, 3H), 6.74 (s, 1H), 4.18-4.12 (m, 3H), 3.97 (s, 3H), 3.96 (s, 3H), 3.99 (s, (m, 3H), 1.23 (d, J=6.3 Hz, 6H). Analysis Calcd for C23H27NO6: C, 66.81; H, 6.58; N, 3.39. Found: C, 66.67; H, 6.65; N, 3.53.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([CH3:14])=[CH:8][C:9](=[O:13])[NH:10]2)=[CH:5][CH:4]=1.[I-].[Na+].[H-].[Li+].Br[CH2:20][CH2:21][CH:22]1[O:26][CH2:25][CH2:24][O:23]1>CN(C)C=O>[O:23]1[CH2:24][CH2:25][O:26][CH:22]1[CH2:21][CH2:20][N:10]1[C:11]2[C:6](=[CH:5][CH:4]=[C:3]([O:2][CH3:1])[CH:12]=2)[C:7]([CH3:14])=[CH:8][C:9]1=[O:13]
Reactant: BrCCC1OCCO1
Reactant: COc1ccc2c(C)cc(=O)[nH]c2c1
Agent: [H-]
Agent: [I-]
Agent: [Li+]
Solvent: CN(C)C=O
Product: COc1ccc2c(C)cc(=O)n(CCC3OCCO3)c2c1
Reaction time: 1 h
Yield: 57 %

Procedure:
In N,N-dimethylformamide (15 ml) was dissolved 7-methoxy-4-methylquinolin-2(1H)one (1.5 g, 6.06 mmol), sodium iodide (2.3 g, 15.9 mmol) was added thereto under cooling on ice and lithium hydride (188 mg, 15.9 mmol) was gradually added thereto. After stirring for 1 hour under cooling on ice, 2-(2-bromoethyl)-1,3-dioxolane (1.6 ml, 15.9 mmol) was gradually added thereto. The reaction solution was stirred overnight at room temperature and then the extract was partitioned into ethyl acetate-water, whereby the organic layer was separated. The obtained organic layer was washed with water and saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and the obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to yield 1 g (57%) of the title compound.
Reaction SMILES: CO[C:3](=[O:31])[CH2:4][CH2:5][C:6]1[C:7]([NH:22][C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])=[N:8][C:9]([S:20][CH3:21])=[N:10][C:11]=1[C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[CH3:19].C[O-].[Na+]>CO>[F:30][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([F:29])[C:23]=1[N:22]1[C:7]2[N:8]=[C:9]([S:20][CH3:21])[N:10]=[C:11]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=3[CH3:19])[C:6]=2[CH2:5][CH2:4][C:3]1=[O:31]
Reactant: COC(=O)CCc1c(Nc2c(F)cccc2F)nc(SC)nc1-c1ccc(F)cc1C
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: CSc1nc(-c2ccc(F)cc2C)c2c(n1)N(c1c(F)cccc1F)C(=O)CC2
Reaction time: 2 h
Yield: 27 %

Procedure:
To a solution of 3-[4-(2,6-difluoro-phenylamino)-6-(4-fluoro-2-methyl-phenyl)-2-methylsulfanyl-pyrimidin-5-yl]-propionic acid methyl ester (45 mg, 0.1 mmol) in methanol (5 mL) was added a solution of sodium methoxide (0.5 mL) and the reaction mixture was heated under reflux for 1 h. The reaction mixture was then evaporated, and EtOAc (20 mL) followed by H2O (10 mL) were added. Layers were separated, organic washed with satd aq NaCl, dried (MgSO4), filtered and the solvent was evaporated. Dichloromethane (5 mL) was added followed by 0.5 mL of oxalyl chloride and 0.1 mL of Et3N. The reaction mixture was then stirred for 2 h at 23°, H2O (5 mL) was then added followed by dichloromethane (15 mL). Layers were separated, organic layer was washed with sat'd aq. NaCl, dried (MgSO4), filtered and solvent was evaporated. The yellow residue was purified by Flash chromatography to give 11.2 mg (21% yield) of pure 8-(2,6-difluoro-phenyl)-4-(4-fluoro-2-methyl-phenyl)-2-methylsulfanyl-5,8-dihydro-6H-pyrido[2,3-d]pyrimidin-7-one. 1H-NMR (CDCl3): δ 2.20 (s, 3H), 2.29 (s, 3H), 3.85 (m, 4H), 7.02 (m, 4H), 7.21 (m, 1H), 7.42 (m, 1H). LC MS (m/e)=416.2 (MH+). Rt=2.44 min.
Reaction SMILES: [N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH:3]([OH:9])[CH2:2]2.[H-].[Na+].F[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[C:19]([F:22])([F:21])[F:20]>CN(C)C=O>[F:20][C:19]([F:22])([F:21])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[O:9][CH:3]1[CH:4]2[CH2:7][CH2:8][N:1]([CH2:6][CH2:5]2)[CH2:2]1
Reactant: Fc1ccccc1C(F)(F)F
Reactant: OC1CN2CCC1CC2
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: FC(F)(F)c1ccccc1OC1CN2CCC1CC2
Temperature: 70 °C
Reaction time: 0.25 h
Yield: 79 %

Procedure:
A solution of 1.78 g (14 mmol) of 3-quinuclidinol in 20 ml of dry N,N-dimethylformamide (DMF) was added dropwise under nitrogen to a suspension of 0.6 g (15 mmol) of sodium hydride in 20 ml of dry DMF. The mixture was stirred for 15 min at 70° C., and a solution of 3.8 ml (30 mmol) of 2-fluoro-(trifluoromethyl)benzene in 8 ml of dry DMF was added dropwise. The mixture was stirred for another 1.5 h, after which the solvent was evaporated. The residue was dissolved in ethyl acetate and washed with brine. The ethyl acetate layer was separated, dried over magnesium sulfate and evaporated to dryness. The crude compound was purified by column chromatography on silica using methanol-dichloromethane (2:8) as eluent to give 3.0 g (59% yield) of 3-[2-(trifluoromethyl)phenoxy]-1-azabicyclo[2.2.2 ]octane, which was converted into the oxalate salt by treatment with oxalic acid and recrystallization from methanol. m.p. 174° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1N)[O:7][CH3:8])([O-:3])=[O:2].[OH-:13].[K+].Cl>O>[N+:1]([C:4]1[CH:5]=[C:6]([O:7][CH3:8])[CH:9]=[CH:10][C:11]=1[OH:13])([O-:3])=[O:2]
Reactant: COc1ccc(N)c([N+](=O)[O-])c1
Reactant: [OH-]
Agent: Cl
Agent: [K+]
Solvent: O
Product: COc1ccc(O)c([N+](=O)[O-])c1
Reaction time: 8 h

Procedure:
A mixture of 168 g. (0.93 m.) of 3-nitro-p-anisidine, 130 g. of KOH and 1500 ml. of H2O was refluxed with stirring overnight. The solution was acidified with conc. HCl, keeping the temperature below 20°C. The crude product was collected by filtration washed with H2O and air-dried to give 279 g. m.p. 74°-76°C. A recrystallization from 2000 ml. of ethanol yields 106 g. m.p.76°-78°C.
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:10][C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[C:21](=[O:22])[NH:20][CH2:19][CH2:18][C:17]=2[C:16]=34)=[CH:5][CH:4]=1.C(Cl)Cl.[OH:26]OS([O-])=O.[K+]>CO.O>[CH3:1][S:2]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[NH:10][C:11]3[CH:12]=[CH:13][CH:14]=[C:15]4[C:21](=[O:22])[NH:20][CH2:19][CH2:18][C:17]=2[C:16]=34)=[CH:5][CH:4]=1)=[O:26]
Reactant: O=S([O-])OO
Reactant: CSc1ccc(-c2[nH]c3cccc4c3c2CCNC4=O)cc1
Agent: [K+]
Solvent: O
Solvent: CO
Solvent: ClCCl
Product: CS(=O)c1ccc(-c2[nH]c3cccc4c3c2CCNC4=O)cc1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
2-(4-methylsulfanyl-phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one (100 mg, 0.32 mmol) was dissolved in 10 mL 1:1 MeOH:CH2Cl2. The solution was cooled to 0° C. and oxone (259 mg, 0.42 mmol) was added dropwise as a solution in 1.5 mL H2O). The bright yellow reaction mixture was stirred at 0° C. for 15 min. Saturated Na2S2O5(aq) (4mL) was added. The layers were separated and the aqueous layer extracted twice with 25% iPrPH/CHCl3. The combined organic layers were dried (MgSO4), concentrated in vacuo, and the two products (2-(4-methanesulfmyl-phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one and 2-(4-methanesulfonyl-phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one) separated by radial chromatography eluting with 5% MeOH/CHCl3. Each was then crystallized from CH2Cl2/MeOH. 2-(4-Methanesulfmyl-phenyl)-1,3,4,5-tetrahydro-azepino[5,4,3-cd]indol-6-one, 39 mg (37%), was isolated as a white solid: m.p. 316-317° C. (dec); 1H NMR (300 MHz, d6-DMSO) 2.81 (s, 3H), 3.09 (m, 2H), 3.40 (m, 2H), 7.25 (t, J=7.8 Hz, 1H), 7.59 (dd, J=8.1, 0.9 Hz, 1H), 7.71 (dd, J=7.5, 0.9 Hz, 1H), 7.84 (m, 4H), 8.08 (br t, 1H), 11.68 (br s, 1H). MS (electrospray, MH+) 325. Anal. (C18H16N2O2S) C, H, N, S.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:10]2[CH:14]=[CH:13][N:12]=[CH:11]2)[CH3:9])=[CH:4][C:3]=1[N+:15]([O-:17])=O.O.[NH2:19][NH2:20].Cl>C(O)CCC>[ClH:1].[N:10]1([CH:8]([C:5]2[CH:6]=[CH:7][C:2]3[N:20]=[N:19][N:15]([OH:17])[C:3]=3[CH:4]=2)[CH3:9])[CH:14]=[CH:13][N:12]=[CH:11]1
Reactant: NN
Reactant: CC(c1ccc(Cl)c([N+](=O)[O-])c1)n1ccnc1
Agent: Cl
Solvent: O
Solvent: CCCCO
Product: CC(c1ccc2nnn(O)c2c1)n1ccnc1
Reaction time: 12 h
Yield: 99 %

Procedure:
A mixture of 4.3 parts of 1-[1(4-chloro-3-nitrophenyl)ethyl]-1H-imidazole, 3.42 parts of hydrazine monohydrate and 40 parts of 1-butanol was stirred for 12 hours at reflux temperature. After cooling, 3.4 parts of a hydrochloric acid solution 10N were added. The separated organic layer was evaporated. The residue was stirred in ethyl acetate. The product was filtered off and dried, yielding 4.5 parts (99.0%) of 6-[1-(1H-imidazol-1-yl)ethyl]-1H-benzotriazol-1-ol monohydrochloride (compound 149).
Reaction SMILES: C(O)(=O)C(O)=O.[Br:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]2[CH2:18][CH2:17][CH2:16][CH:15]2[NH2:19])=[CH:10][CH:9]=1.C1CCN2C(=NCCC2)CC1.[CH:31]([S:34](Cl)(=[O:36])=[O:35])([CH3:33])[CH3:32]>C(Cl)Cl>[Br:7][C:8]1[CH:9]=[CH:10][C:11]([C@H:14]2[CH2:18][CH2:17][CH2:16][C@H:15]2[NH:19][S:34]([CH:31]([CH3:33])[CH3:32])(=[O:36])=[O:35])=[CH:12][CH:13]=1
Reactant: NC1CCCC1c1ccc(Br)cc1
Reactant: CC(C)S(=O)(=O)Cl
Agent: O=C(O)C(=O)O
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: CC(C)S(=O)(=O)N[C@@H]1CCC[C@@H]1c1ccc(Br)cc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A 100 mL round bottom flask equipped with a magnetic stirrer was charged with (+,−) cis-[2-(4-bromo-phenyl)-cyclopentylamine oxalate salt (500 mg, 1.51 mmol), methylene chloride (5.0 mL) and the solution was cooled to 0° C. DBU (1.8 mL, 12.1 mmol) and isopropylsulfonyl chloride (1.02 mL, 9.06 mmol) were added. The reaction was then stirred at 0° C. for 60.0 minutes and brought to room temperature with stirring overnight. The reaction was diluted with methylene chloride and washed with 1N HCl, brine and the organic layer dried over sodium sulfate. The title compound was purified by radial chromatography eluting with methylene chloride to give 233 mg (45%) of the purified title compound. The nmr was consistent with the assigned structure.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6].[CH:7]([NH2:10])([CH3:9])[CH3:8]>>[CH:7]([NH:10][CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6])([CH3:9])[CH3:8]
Reactant: C=CCCCBr
Reactant: CC(C)N
Product: C=CCCCNC(C)C
Temperature: 60 °C
Reaction time: 48 h
Yield: 40 %

Procedure:
5-Bromo-1-pentene (42.3 mmol) was added to isopropylamine (423 mmol), and the mixture was stirred at 60° C. for 48 h in the dark in a sealed tube. Then the volatiles were evaporated at reduced pressure and the crude residue was dissloved in 50 mL of diethyl ether and washed twice with water. The organic phase was dried over Na2SO4. Evaporation of the solvent gave N-isopropylpent-4-en-1-amine as brownish oil (40%) which was used without any further purification.