Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: OO.C(OC(C(F)(F)F)=O)(C(F)(F)F)=[O:4].[CH3:16][O:17][CH:18]1[CH2:21][N:20]([CH2:22][CH2:23][CH2:24][C:25]2[N:26]=[N+:27]([O-:38])[C:28]3[CH:37]=[C:36]4[C:32]([CH2:33][CH2:34][CH2:35]4)=[CH:31][C:29]=3[N:30]=2)[CH2:19]1.C(O)(C(F)(F)F)=O>C(Cl)Cl.N>[CH3:16][O:17][CH:18]1[CH2:21][N:20]([CH2:22][CH2:23][CH2:24][C:25]2[N:26]=[N+:27]([O-:38])[C:28]3[CH:37]=[C:36]4[C:32]([CH2:33][CH2:34][CH2:35]4)=[CH:31][C:29]=3[N+:30]=2[O-:4])[CH2:19]1
Reactant: COC1CN(CCCc2nc3cc4c(cc3[n+]([O-])n2)CCC4)C1
Reactant: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Agent: N
Agent: OO
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC1CN(CCCc2n[n+]([O-])c3cc4c(cc3[n+]2[O-])CCC4)C1
Temperature: 0 °C
Reaction time: 0.08 h
Yield: 60.5 %

Procedure:
H2O2 (70%, 2.0 mL, 39 mmol) was added dropwise to a stirred solution of TFAA (5.4 mL, 39 mmol) in DCM (50 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 82 (0.93 g, 3.0 mmol) and TFA (1.5 mL, 19.5 mmol) in DCM (50 mL) at 0° C. The solution was stirred at 20° C. for 8 h, diluted with dilute aqueous NH3 solution (30 mL) and extracted with DCM (3×150 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH/DCM, to give 1,4-dioxide 83 (0.60 g, 60%) as a red gum: 1H NMR δ 8.31 (s, 1H, H-9), 8.28 (s, 1H, H-5), 4.60-4.70 (m, 2H, CH2N), 4.33-4.40 (m, 1H, CHO), 3.60-3.75 (m, 2H, CH2N), 3.33 (s, 3H, CH3O), 3.25-3.32 (m, 2H, CH2N), 3.12-3.25 (m, 6H, H-6, H-8, CH2), 2.27-2.33 (m, 4H, H-7, CH2); 13C NMR δ 155.5, 152.3, 151.2, 139.1, 134.1, 115.9, 113.9, 67.8, 61.0, 58.9, 56.9, 55.6, 32.9, 32.4, 26.9, 25.6, 22.9; HRMS (FAB+) calcd for C17H23N4O3 (MH+) m/z 331.1770, found 331.1771.
Reaction SMILES: [F:1][C:2]1[CH:16]=[C:15](B2OC(C)(C)C(C)(C)O2)[CH:14]=[CH:13][C:3]=1[O:4][C:5]1[C:6]([CH3:12])=[N:7][C:8]([CH3:11])=[CH:9][CH:10]=1.C([O-])(O)=O.[Na+].Br[C:32]1[CH:37]=[CH:36][N:35]([CH2:38][CH2:39][CH2:40][CH3:41])[C:34](=[O:42])[C:33]=1[C:43]#[N:44]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:38]([N:35]1[CH:36]=[CH:37][C:32]([C:15]2[CH:14]=[CH:13][C:3]([O:4][C:5]3[C:6]([CH3:12])=[N:7][C:8]([CH3:11])=[CH:9][CH:10]=3)=[C:2]([F:1])[CH:16]=2)=[C:33]([C:43]#[N:44])[C:34]1=[O:42])[CH2:39][CH2:40][CH3:41]
Reactant: Cc1ccc(Oc2ccc(B3OC(C)(C)C(C)(C)O3)cc2F)c(C)n1
Reactant: CCCCn1ccc(Br)c(C#N)c1=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Product: CCCCn1ccc(-c2ccc(Oc3ccc(C)nc3C)c(F)c2)c(C#N)c1=O
Yield: 51.7 %

Procedure:
To a solution of intermediate 12 (2 mmol) in 1,4-dioxane (6 ml) and a saturated solution of NaHCO3 (6 ml) was added intermediate 6 (0.51 g, 2 mmol). The resulting solution was degassed using a stream of nitrogen and to this was added Pd(PPh3)4 (0.231 mg, 0.2 mmol). The reaction was then microwaved in a sealed tube at 150° C. for 10 minutes. The resulting cooled reaction mixture was filtered through a pad of diatomaceous earth and concentrated in vacuo. The crude reaction mixture was then purified by column chromatography (silica gel; DCM to DCM/MeOH up to 3% as eluent). The desired fractions were collected and evaporated in vacuo to yield compound 2 (0.405 g, 52%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:10])=[C:6]([CH2:8][OH:9])[CH:7]=1.[C:11](=[O:14])([O-])[O-:12].[Na+].[Na+]>O1CCOCC1.O>[Cl:10][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:11](=[O:14])[O:12][C:6]([CH3:8])([CH3:7])[CH3:5])=[CH:7][C:6]=1[CH2:8][OH:9]
Reactant: O=C([O-])[O-]
Reactant: Nc1ccc(Cl)c(CO)c1
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)Nc1ccc(Cl)c(CO)c1
Reaction time: 3 h
Yield: 136.9 %

Procedure:
To a solution of (5-amino-2-chlorophenyl)methanol (Aldrich, 500 mg, 3.17 mmol) in a mixture of dioxane (7.5 mL), water (7.5 mL) was added sodium carbonate (336 mg, 3.17 mmol) previously dissolved in 4 mL of water. Solution was stirred and cooled in an ice bath. Boc-anhydride (Aldrich, 692 mg, 3.17 mmol) was added in one portion, and stirring was continued at room temperature for 3 h. Dioxane was removed in vacuo conditions and the aqueous layer chilled, covered with a layer of ethyl acetate, and acidified to pH 4 with dilute KHSO4 (10%, aq) (ALDRICH). This was followed by extraction (EtOAc) and purification by chromatographic column 25 g cartridge (ISOLUTE silice) using Hex/EtOAc 100/0 to 50/50, giving 1,1-dimethylethyl [4-chloro-3-(hydroxymethyl)phenyl]carbamate (560 mg, 2.17 mmol, 68%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 9.46 (br s, 1H), 7.72 (s, 1H), 7.21-7.32 (m, 2H), 5.35 (t, 1H), 4.48 (d, 2H), 1.47 (s, 9H).
Reaction SMILES: [N:1]([CH:4]1[C:10](=[O:11])[N:9]2[CH:5]1[CH2:6][C:7](OS(C1C(C)=CC=CC=1)(=O)=O)=[C:8]2[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])=[N+:2]=[N-:3].[CH3:33][N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.C(N(CC)CC)C.CN(C)C=O>C(OC(=O)C)C>[N:1]([CH:4]1[C:10](=[O:11])[N:9]2[CH:5]1[CH2:6][C:7]([CH:35]1[CH2:36][NH:37][CH2:38][CH2:39][N:34]1[CH3:33])=[C:8]2[C:12]([O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:13])=[N+:2]=[N-:3]
Reactant: Cc1ccccc1S(=O)(=O)OC1=C(C(=O)OCc2ccccc2)N2C(=O)C(N=[N+]=[N-])C2C1
Reactant: CN1CCNCC1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CN1CCNCC1C1=C(C(=O)OCc2ccccc2)N2C(=O)C(N=[N+]=[N-])C2C1
Reaction time: 8 h

Procedure:
A mixture of benzyl 6-azido-3-toluenesulfonyloxy-1-azabicyclo[3.2.0]hept-2-en-7-one-2-carboxylate (0.1 mmol), N-methylpiperazine (0.11 mmol), triethylamine (1 mmol) and anhydrous dimethylformamide (1 ml) is allowed to stand at room temperature overnight. The mixture is diluted with ethylacetate, washed thoroughly with water and brine, dried over magnesium sulfate, and filtered. Evaporation of the solvent under vacuum provides benzyl 6-azido-3-(N-methylpiperazinyl)1-azabicyclo[3.2.0]-hept-2-en-7-one-2-carboxylate.
Reaction SMILES: NC1C=C2C(=CC=1)N=CC=C2.[OH:12][N:13]=[CH:14][C:15]([NH:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[N:24]=[CH:23][CH:22]=[CH:21]2)=[O:16].S(=O)(=O)(O)[OH:29]>>[OH:12][N:13]=[CH:14][C:15]([NH:17][C:18]1[CH:19]=[C:20]2[C:25](=[CH:26][CH:27]=1)[N:24]=[CH:23][CH:22]=[CH:21]2)=[O:16].[C:14]1(=[O:29])[C:19]2=[C:20]3[C:25](=[CH:26][CH:27]=[C:18]2[NH:17][C:15]1=[O:16])[N:24]=[CH:23][CH:22]=[CH:21]3
Reactant: O=S(=O)(O)O
Agent: Nc1ccc2ncccc2c1
Agent: O=C(C=NO)Nc1ccc2ncccc2c1
Product: O=C1Nc2ccc3ncccc3c2C1=O
Reaction time: 1 h
Yield: 31 %

Procedure:
2-Hydroxyimino-N-quinolin-6-yl-acetamide was prepared in 61% yield from 6-aminoquinoline according to Procedure A: 1H NMR (DMSO-d6): δ12.4 (s,1H), 10.8 (s, 1H), 9.0 (d, 1H), 8.8 (d, 1H), 8.7 (s, 1H), 8.2 (s, 2H), 7.81 (m, 1H), 7.78 (s, 1H); C11H9N3O2: APCI−MS m/z 216 (M+H)+. To a 1-L 3-neck round bottom flask was placed a magnetic stir bar and 110 mL of concentrated sulfuric acid. The flask was fitted with a thermometer to monitor the temperature of the reaction. The sulfuric acid was heated to 100° C. followed by slow addition of 2-hydroxyimino-N-quinolin-6-yl-acetamide (26.0 g, 0.121 mol). Heat to the reaction was maintained for approximately 1 h. The flask was removed from the heat source, and the reaction was poured slowly and carefully onto a mixture of 1 Kg of ice and 200 g of sodium carbonate. The residual reaction mixture in the reaction vessel was washed out with an additional 40 mL of cold water. The resulting aqueous slurry was stirred for about 1 h and filtered. The solid was washed thoroughly with water, filtered, and air dried to yield 7.31 g (31%) of 3-H-pyrrolo[3,2-f]quinoline-1,2-dione: 1H NMR (DMSO-d6): δ11.1 (s, 1H), 8.8 (d, 1H), 8.7 (d, 1H), 8.2 (d, 1H), 7.6 (m, 1H), 7.4 (d, 1H); APCI−MS m/z 197 (M−H)−. The title compound was prepared in 77% yield from 3-H-pyrrolo[3,2-f]quinoline-1,2-dione and 4-hydrazinophenylmethane sulfonamide according to Procedure G: 1H NMR (DMSO-d6): δ13.1 (s, 1H), 11.5 (s, 1H), 9.3 (d, 1H), 8.9 (d, 1H), 8.0 (d, 1H), 7.9 (m, 1H), 7.6 (d, 1H), 7.6(d, 2H), 7.4 (d, 2H), 6.9(d, 1H), 4.3 (s, 2H), 2.55 (d, 3H); APCI−MS m/z 396 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]3[C:13]([NH2:18])=[N:14][CH:15]=[C:16](I)[C:11]=3[S:10][CH:9]=2)=[CH:4][CH:3]=1.[CH2:19]([N:22]1[C:26](=[O:27])[C:25]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]2[C:23]1=[O:32])[C:20]#[CH:21].O>CN(C=O)C.C(N(CC)CC)C.[Cu]I>[NH2:18][C:13]1[C:12]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=3)=[CH:9][S:10][C:11]=2[C:16]([C:21]#[C:20][CH2:19][N:22]2[C:26](=[O:27])[C:25]3[C:24](=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:23]2=[O:32])=[CH:15][N:14]=1
Reactant: C#CCN1C(=O)c2ccccc2C1=O
Reactant: Nc1ccc(-c2csc3c(I)cnc(N)c23)cc1
Agent: [Cu]I
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: Nc1ccc(-c2csc3c(C#CCN4C(=O)c5ccccc5C4=O)cnc(N)c23)cc1
Temperature: 80 °C
Yield: 43.4 %

Procedure:
A suspension of Example 77B (0.6 g, 1.63 mmol) in DMF (3 mL) and triethylamine (2 mL) was degassed by bubbling nitrogen through the suspension for 5 minutes, treated with N-propargylphthalimide (0.45 g, 2.45 mmol), PdCl2(PPh3)4 (57 mg, 0.08 mmol), and CuI (15 mg, 0.08 mmol), then heated to 80° C. for 1 hour. The cooled solution was poured into water, extracted with ethyl acetate and the combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography on silica gel using 3% methanol/dichloromethane to provide 300 mg (43% yield) of the desired product.
Reaction SMILES: [C:1]1([C:7]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:19][O:20][NH2:21].CCOC(C)=O>N1C=CC=CC=1>[CH3:19][O:20][N:21]=[C:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:9]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][CH:10]=1
Reactant: O=C(c1ccccc1)c1ccc(C(F)(F)F)cc1
Reactant: CON
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: CON=C(c1ccccc1)c1ccc(C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.3 %

Procedure:
To a 100-mL round-bottomed flask, phenyl(4-(trifluoromethyl)phenyl)-methanone (1.0105 g, 4.039 mmol) and methoxyamine (0.4208 g, 5.038 mmol) were dissolved in pyridine (10 mL). The mixture was stirred at rt overnight. Additional methoxyamine (0.1625 g) was added, and the solution was stirred at rt for 7 h. EtOAc was added and the organic phase was washed with water, 1 N HCl (2×), water, and then with brine. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford a clear oil. The oil thus obtained was purified by Biotage (EtOAc/hexanes 0-20%) to afford the title compound (1.12 g, 99.4%) as a clear oil.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6]Cl)=[C:4]([F:10])[CH:3]=1.C(O)C.[C-:14]#[N:15].[Na+]>O>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][C:14]#[N:15])=[C:4]([F:10])[CH:3]=1
Reactant: [C-]#N
Reactant: Fc1cc(Cl)ccc1CCl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: N#CCc1ccc(Cl)cc1F
Temperature: 25 °C
Yield: 86.2 %

Procedure:
Then, 18.5 g of 4-chloro-2-fluorobenzyl chloride was dissolved in a mixed solvent consisting of 130 ml of ethanol and 30 ml of water, to which 5.3 g of sodium cyanide was added, and the mixture was heated under reflux for 2 hours. After completion of the reaction, the reaction mixture was allowed to stand for cooling to room temperature, poured into water, and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 15.1 g of 4-chloro-2-fluorophenylacetonitrile.
Reaction SMILES: CS(O[CH2:6][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([Br:15])=[CH:11][CH:10]=1)(=O)=O.[N:16]1([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.C(N(CC)CC)C>C(#N)C>[Br:15][C:12]1[CH:13]=[CH:14][C:9]([CH2:8][CH2:7][CH2:6][N:19]2[CH2:18][CH2:17][N:16]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:21][CH2:20]2)=[CH:10][CH:11]=1
Reactant: CS(=O)(=O)OCCCc1ccc(Br)cc1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CC(C)(C)OC(=O)N1CCN(CCCc2ccc(Br)cc2)CC1
Temperature: 75 °C

Procedure:
To a stirred solution of 3-(4-bromophenyl)propyl methanesulfonate (4.2 g, 14.33 mmol) in acetonitrile (33.2 ml) was added tert-butyl piperazine-1-carboxylate (3.47 g, 18.62 mmol) and triethylamine (2.60 ml, 18.62 mmol). Reaction mixture heated to 75° C. overnight. The reaction mixture was evaporated to dryness and redissolved in EtOAc (40 mL), and washed with 2:8 saturated brine:water (45 mL). The aqueous was extracted with EtOAc (2×25 mL), organics combined and washed with 2:8 saturated brine:water (2×45 mL) and saturated brine (25 mL). The organic was dried over magnesium sulfate, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography using Isco Companion, 50 g silica column, elution gradient 30 to 50% EtOAc in dichloromethane. Pure fractions were evaporated to dryness to afford the sub-title compound as a yellow oil. Yield: 2.4 g
Reaction SMILES: [C:1]1([N:7]2[CH2:12][CH2:11][N:10]([CH2:13][CH2:14][O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[CH:22]3[NH:26][CH2:25][CH2:24][S:23]3)[CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:27][N:28]=[C:29]=[O:30]>O1CCCC1>[CH3:27][NH:28][C:29]([N:26]1[CH2:25][CH2:24][S:23][CH:22]1[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[O:15][CH2:14][CH2:13][N:10]1[CH2:11][CH2:12][N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:8][CH2:9]1)=[O:30]
Reactant: CN=C=O
Reactant: c1ccc(N2CCN(CCOc3ccccc3C3NCCS3)CC2)cc1
Solvent: C1CCOC1
Product: CNC(=O)N1CCSC1c1ccccc1OCCN1CCN(c2ccccc2)CC1
Reaction time: 2 h
Yield: 89.7 %

Procedure:
3.69 g of 2-{2-[2-(4-phenylpiperazin-1-yl)ethyloxy]phenyl}thiazolidine are dissolved in 40 ml of tetrahydrofuran, and 0.62 g of methyl isocyanate is added thereto at room temperature. The mixture is stirred at the same temperature for 2 hours. The mixture is concentrated under reduced pressure to remove solvent. Water is added to the residue, and crystalline precipitates are collected by filtration. The crystals are washed with ethanol and ether, and then recrystallized from a mixture of ethyl acetate and n-hexane. 3.82 g of N-methyl-2-{2-[2-(4-phenylpiperazin-1-yl)ethyloxy]phenyl}thiazolidin-3-carboxamide are obtained. Yield: 89.7%.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH2:13][C@@H:14]([O:16][CH3:17])[CH3:15])[N:8]=[C:7]([CH3:18])[CH:6]=[CH:5]2.[O:19]1CCOCC1>O>[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH2:13][C@@H:14]([O:16][CH3:17])[CH3:15])[N:8]=[C:7]([CH:18]=[O:19])[CH:6]=[CH:5]2
Reactant: CO[C@@H](C)COc1cc2nc(C)ccc2cc1F
Reactant: C1COCCO1
Solvent: O
Product: CO[C@@H](C)COc1cc2nc(C=O)ccc2cc1F
Yield: 85 %

Procedure:
To a solution of crude (S)-6-fluoro-7-(2-methoxypropoxy)-2-methylquinoline (0.281 g, 1.13 mmol) in dioxane (4 mL) and water (0.04 mL) was added SeO2 (0.138 g, 1.24 mmol). The reaction mixture was heated at reflux for 3 hours. After cooling, the mixture was filtered through Celite®. The filtrate was concentrated. The residue was purified by flash chromatography on silica gel (hexanes:EtOAc, 4:1) to give (S)-6-fluoro-7-(2-methoxypropoxy)quinoline-2-carbaldehyde (0.251 g, 85% for two steps) as a solid.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C@H:12]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:13]([OH:15])=[O:14])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Na][Na].Cl.[C:26]1([CH:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>>[C:17]1([CH2:16][C@@H:12]([NH:11][S:8]([C:5]2[CH:6]=[CH:7][C:2]([N:35]3[CH2:36][CH2:37][CH:32]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH2:33][CH2:34]3)=[CH:3][CH:4]=2)(=[O:10])=[O:9])[C:13]([OH:15])=[O:14])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: c1ccc(C2CCNCC2)cc1
Reactant: O=C(O)[C@@H](Cc1ccccc1)NS(=O)(=O)c1ccc(F)cc1
Agent: Cl
Agent: [Na][Na]
Product: O=C(O)[C@@H](Cc1ccccc1)NS(=O)(=O)c1ccc(N2CCC(c3ccccc3)CC2)cc1

Procedure:
In a manner similar to Example 3(b), (R)-2-(4-fluoro-benzenesulfonylamino)-3-phenyl-propionic acid, disodium salt was condensed with 4-phenyl-piperidine hydrochloride to give the title compound, mp=168-170° C.
Reaction SMILES: [NH:1]1[C:9]2[C:4]3[C:5](=[CH:10][CH:11]=[CH:12][C:3]=3[C:2]1=[O:13])[CH:6]=[CH:7][CH:8]=2.[H-].[Na+].CI.[C:18](OCC)(=O)C>CN(C)C=O.O>[CH3:18][N:1]1[C:9]2[C:4]3[C:5](=[CH:10][CH:11]=[CH:12][C:3]=3[C:2]1=[O:13])[CH:6]=[CH:7][CH:8]=2
Reactant: CCOC(C)=O
Reactant: O=C1Nc2cccc3cccc1c23
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: O
Solvent: CN(C)C=O
Product: CN1C(=O)c2cccc3cccc1c23
Reaction time: 0.33 h

Procedure:
Benz[cd]indole-2(1H)-one (5.1 g, 30 mmol) was dissolved in anhydrous N,N-dimethylformamide (100 ml). Thereto was added sodium hydride (60% content, 1.2 g, 30 mmol), and the resulting solution was stirred for 20 minutes in an ice bath. The reaction solution was mixed with methyl iodide (2.6 ml, 42 mmol) and again stirred at a room temperature for 1 hour. The reaction solution was mixed with ethyl acetate (300 ml) and water (200 ml), and the reaction product was extracted with ethyl acetate. The ethyl acetate layer was separated, washed with water and then dried with anhydrous sodium sulfate. By evaporating ethyl acetate under a reduced pressure, 4.7 g (26 mmol, 74% in yield) of the title compound was obtained as yellow crystals.
Reaction SMILES: [N+:1]([C:4]1[CH:8]=[CH:7][N:6]([CH2:9][C@@H:10]([OH:13])[CH2:11][OH:12])[N:5]=1)([O-])=O.[H][H]>[Pd].C(O)C>[NH2:1][C:4]1[CH:8]=[CH:7][N:6]([CH2:9][C@@H:10]([OH:13])[CH2:11][OH:12])[N:5]=1
Reactant: O=[N+]([O-])c1ccn(C[C@@H](O)CO)n1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: Nc1ccn(C[C@@H](O)CO)n1
Yield: 97.6 %

Procedure:
In a Parr shaker bottle was placed (R)-3-(3-nitro-pyrazol-1-yl)-propane-1,2-diol (3.17 g, 16.95 mmol), 10% palladium on activated carbon (200 mg) and ethanol (30 mL). The bottle was then placed on the Parr shaker at 50 psi of hydrogen pressure for 5 h. The reaction was then filtered through a pad of celite and washed with ethanol and concentrated in vacuo to afford (R)-3-(3-amino-pyrazol-1-yl)-propane-1,2-diol (2.60 g, 98%) as a yellow oil: LR-ES-MS m/z calculated for C6H11N3O2 [M]+ 157, observed [M+H]+ 158.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1([CH2:18][N:19]2[CH:23]=[N:22][CH:21]=[N:20]2)[NH:13][CH:12]([C:14]([O:16]C)=O)[CH2:11][S:10]1.[CH2:24]([NH2:27])[CH2:25][CH3:26]>CO>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1([CH2:18][N:19]2[CH:23]=[N:22][CH:21]=[N:20]2)[NH:13][CH:12]([C:14]([NH:27][CH2:24][CH2:25][CH3:26])=[O:16])[CH2:11][S:10]1
Reactant: CCCN
Reactant: COC(=O)C1CSC(Cn2cncn2)(c2ccc(Cl)cc2Cl)N1
Solvent: CO
Product: CCCNC(=O)C1CSC(Cn2cncn2)(c2ccc(Cl)cc2Cl)N1
Yield: 39.9 %

Procedure:
1.87 g of 2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazole-1-yl methyl)-4-methoxycarbonyl thiazolidine (Compound No. 24) prepared in the same manner as in Working Example 2 and 3.0 g of n-propylamine were dissolved in 20 ml of methanol and reacted at a temperature of 60° C. for 1 hour. After distilling off methanol under reduced pressure, the reaction product was purified by silica gel column chromatography using a solvent mixture of chloroform and ethyl acetate as the developer, whereby 0.8 g of 2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazole-1-yl methyl)-4-(n-propylaminocarbonyl)thiazolidine (Compound No. 46 in Table 1) was obtained.
Reaction SMILES: [OH-].[Na+].[CH2:3]([CH:5]([CH2:8][CH3:9])[CH:6]=[O:7])[CH3:4].[Cl:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15]Cl)=[CH:13][CH:12]=1>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[Cl:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15][C:5]([CH2:8][CH3:9])([CH2:3][CH3:4])[CH:6]=[O:7])=[CH:13][CH:12]=1
Reactant: ClCc1ccc(Cl)cc1
Reactant: CCC(C=O)CC
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCC(C=O)(CC)Cc1ccc(Cl)cc1

Procedure:
300 ml of toluene, 400 ml of 30 percent (by weight) sodium hydroxide solution and 5.0 g of tetra-n-butyl-ammonium iodide are heated at 80° C. while stirring. To this is slowly added dropwise a mixture of 110 g (1.10 mol) of 2-ethylbutanal and 161 g (1.00 mol) of 4-chlorobenzyl chloride. The mixture is then stirred at 80° C. for 4 h and at room temperature for 14 h, 1,000 ml of toluene are added, and the phases are separated. The organic phase is washed with water, dried over Na2SO4 and concentrated. Fractional distillation results in 123 g (54% of theory) of 2-(4-chlorobenzyl) -2-ethylbutanal as a colorless liquid of boiling point 146°-148° C. at 1 mbar.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.CCCCCC.[CH2:19]([N:26]1[CH2:31][CH2:30][CH:29]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:28][CH2:27]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[CH3:37][C:38]([O:41][C:42](/[N:44]=[N:45]/[C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])=[O:43])([CH3:40])[CH3:39].C(=O)([O-])[O-].[K+].[K+]>CCOCC>[CH2:19]([N:26]1[CH2:31][CH2:30][C:29]([C:32]([O:34][CH2:35][CH3:36])=[O:33])([N:44]([C:42]([O:41][C:38]([CH3:40])([CH3:39])[CH3:37])=[O:43])[NH:45][C:46]([O:48][C:49]([CH3:50])([CH3:51])[CH3:52])=[O:47])[CH2:28][CH2:27]1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CCOC(=O)C1CCN(Cc2ccccc2)CC1
Reactant: CC(C)(C)OC(=O)/N=N/C(=O)OC(C)(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: CCOCC
Solvent: CC(C)NC(C)C
Product: CCOC(=O)C1(N(NC(=O)OC(C)(C)C)C(=O)OC(C)(C)C)CCN(Cc2ccccc2)CC1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 54.1 %

Procedure:
A solution of diisopropylamine (8.8 ml, 0.063 mol) in ether (400 ml) at -70° C. under nitrogen was treated with 1.6M n-butyllithium in hexane (37.5 ml, 0.060 mol) and stirred for 10 minutes. A solution of ethyl 1-benzylpiperidin-4-ylcarboxylate (13.6 g, 0.055 mol) in ether (70 ml) was added over 5 minutes and the resulting mixture then stirred at -70° C. for 40 minutes, before adding a solution of di-tert-butylazodicarboxylate (13.5 g, 0.058 mol) in ether (80 ml). The reaction mixture was allowed to warm to room temperature over 0.5 h, then stirred for a further 2 h before adding dilute potassium carbonate solution (150 ml). The ether layer was separated, dried (Na2SO4) and concentrated in vacuo to leave an orange oil. This was chromatographed on silica gel eluting initially with 20% ether/60-80 petrol, then with neat ether to afford the title compound (D26) (14.2 g, 54%) as a yellow oil.