Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[O:3]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH2:5][CH:4]1[CH:12]1[C:24]2[NH:23][C:22]3[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=3)[C:16]=2[CH2:15][CH2:14][N:13]1[C:25]1[N:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][N:32]=2)=[CH:27][N:26]=1.CN(C=[O:41])C>>[N:32]1[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=1[C:28]1[CH:29]=[N:30][C:25]([N:13]2[CH2:14][C:15]3[C:16](=[O:41])[C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=4[NH:23][C:24]=3[CH:12]2[CH:4]2[CH2:5][CH:6]3[CH2:11][CH:10]=[CH:9][CH:8]=[C:7]3[O:3]2)=[N:26][CH:27]=1
Reactant: c1ccc(-c2cnc(N3CCc4c([nH]c5ccccc45)C3C3Cc4ccccc4O3)nc2)nc1
Reactant: CN(C)C=O
Agent: [H-]
Agent: [Na+]
Product: O=c1c2c([nH]c3ccccc13)C(C1CC3CC=CC=C3O1)N(c1ncc(-c3ccccn3)cn1)C2

Procedure:
Sodium hydride (60% in mineral oil, 182 mg, 4.55 mmol) and 1-(2,3-dihydro-5-benzofuranyl)-2,3,4,9-tetrahydro-2-[5-(2-pyridinyl)-2-pyrimidinyl]-1H-β-carboline (16176-23) (882 mg, 1.98 mmol) (prepared as in Example 49) in DMF (30 mL, anhydrous) were stirred at room temperature for 30 min. Dry air then was bubbled through the reaction mixture for 16 h. Ethyl acetate (200 mL) was added, and the resulting mixture was washed with 10% NaCl solution, brine, and then dried with MgSO4. The reaction mixture solvent was evaporated and the residue triturated with ethyl acetate to yield the product as a white solid.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])[C:5]([O:7][CH3:8])=[O:6].O.[CH3:17][N:18](C=O)C>[C-]#N.[Zn+2].[C-]#N.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:17]([C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])[C:5]([O:7][CH3:8])=[O:6])#[N:18]
Reactant: CN(C)C=O
Reactant: COC(=O)c1ccc(OC(C)C)c(Br)c1
Agent: [Fe+2]
Agent: [C-]#N
Agent: [Zn+2]
Solvent: O
Product: COC(=O)c1ccc(OC(C)C)c(C#N)c1
Temperature: 120 °C
Reaction time: 48 h

Procedure:
A mixture of 1.32 g (4.83 mmol) of methyl 3-bromo-4-isopropyloxybenzoate (from Step B), 341 mg (2.90 mmol) of zinc cyanide, 67 mg (0.12 mmol) of 1,1′-bis(diphenylphosphino)ferrocene, 44 mg (0.05 mmol) of tris(dibenzylideneacetone) dipalladium(0)-chloroform complex and 50 μL of H2O in 5.0 mL of DMF was stirred at 120° C. for 48 h. The mixture was cooled, then partitioned between EtOAc and sat'd NaCl. The aqueous layer was separated and extracted with 3× EtOAc. The organic layers were combined, dried over MgSO4 and concentrated. Chromatography on a Biotage 40M cartridge using 9:1 v/v hexanes/EtOAc gave 802 mg of the title compound: 1H NMR (500 MHz, CDCl3) δ 1.44 (d, J=6.2, 6H), 3.91 (s, 3H), 4.71-4.79 (m, 1H), 6.99 (d, J=8.9, 1H), 8.18 (dd, J=2.2, 8.8, 1H), 8.24 (d, J=2.1, 1H).
Reaction SMILES: [CH2:1]([O:4][CH2:5][C@H:6]([NH:13][CH2:14][C@@H:15]([OH:37])[C@@H:16]([NH:26]C(=O)OCC1C=CC=CC=1)[CH2:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH:2]=[CH2:3]>COCCOC.O>[CH2:1]([O:4][CH2:5][C@H:6]([NH:13][CH2:14][C@@H:15]([OH:37])[C@@H:16]([NH2:26])[CH2:17][C:18]1[CH:19]=[C:20]([F:25])[CH:21]=[C:22]([F:24])[CH:23]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH:2]=[CH2:3]
Reactant: C=CCOC[C@H](NC[C@@H](O)[C@H](Cc1cc(F)cc(F)c1)NC(=O)OCc1ccccc1)c1ccccc1
Solvent: O
Solvent: COCCOC
Product: C=CCOC[C@H](NC[C@@H](O)[C@@H](N)Cc1cc(F)cc(F)c1)c1ccccc1
Temperature: 110 °C
Reaction time: 18 h
Yield: 68 %

Procedure:
Step Q (5): A mixture of benzyl (2S,3R)-4-((R)-2-(allyloxy)-1-phenylethylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-ylcarbamate (1.1 g, 2.15 mmol) from step Q (4), Ba(OH)2.H2O (1.23 g, 6.47 mmol), and DME/H2O (12 mL/8 mL) was heated at 110° C. in a sealed tube. After 18 h, the vessel was cooled to rt and the precipitate was removed by filtration. The vessel and filtercake were rinsed with fresh DME and the combined filtrates were concentrated in vacuo. The crude product was purified by silica gel chromatography to give 550 mg (68% yield) of the title compound as a yellow viscous oil. LC-MS (M+H)+=377.4; 1H NMR (300 MHz, CDCl3) δ ppm 2.46-3.01 (m, 3H) 3.13-3.72 (m, 7H) 3.89-4.04 (m, 2H) 5.10-5.28 (m, 2H) 5.77-5.96 (m, 1H) 6.52-6.78 (m, 3H) 7.24-7.41 (m, 4H).
Reaction SMILES: [Cl:1][C:2]1[CH:28]=[N:27][C:5]2[NH:6][C:7]3[C:8](OC)([OH:24])[CH2:9][CH:10]=[C:11]([C:13]4[CH:18]=[CH:17][CH:16]=[C:15]([S:19]([CH2:22][CH3:23])(=[O:21])=[O:20])[CH:14]=4)[C:12]=3[C:4]=2[CH:3]=1.C(S(C1C=C(C2C=CC(O)=C3C=2C2C=C(C)C=NC=2N3)C=CC=1)(=O)=O)C>>[Cl:1][C:2]1[CH:28]=[N:27][C:5]2[NH:6][C:7]3[C:12]([C:4]=2[CH:3]=1)=[C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([S:19]([CH2:22][CH3:23])(=[O:21])=[O:20])[CH:14]=1)[CH:10]=[CH:9][C:8]=3[OH:24]
Reactant: CCS(=O)(=O)c1cccc(C2=CCC(O)(OC)c3[nH]c4ncc(Cl)cc4c32)c1
Agent: CCS(=O)(=O)c1cccc(-c2ccc(O)c3[nH]c4ncc(C)cc4c23)c1
Product: CCS(=O)(=O)c1cccc(-c2ccc(O)c3[nH]c4ncc(Cl)cc4c23)c1

Procedure:
The title compound was prepared from Compound 217 by using an analogous procedure to that outlined in the preparation of Compound 157. 1H NMR (400 MHz, Methanol-d4) δ 8.35 (s, 1H) 8.15 (m, 1H) 8.07 (m, 1H) 7.97 (m, 1H) 7.88 (t, J=8.0 Hz, 1H) 7.66 (s, 1H) 7.23 (d, J=8.36 Hz, 1H) 7.16 (d, J=8.36 Hz, 1H) 4.44 (t, J=5.8 Hz, 2H) 3.72 (t, J=8.0 Hz, 2H) 3.43 (q, J=7.32 Hz, 2H) 3.03 (s, 6H) 2.41 (m, 2H) 1.34 (t, J=7.32 Hz, 3H). [M+H] calc'd for C24H27ClN3O3S, 472; found, 472.
Reaction SMILES: [OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.Br[CH2:11][CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15]>>[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:11][CH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:5][CH:4]=1
Reactant: CCOC(=O)CCCBr
Reactant: OCc1ccc(O)cc1
Product: CCOC(=O)CCCOc1ccc(CO)cc1

Procedure:
Ethyl 4-(4-(hydroxymethyl)phenoxy)butanoate 29b was prepared by reacting 4-(hydroxymethyl)phenol 27b with ethyl 4-bromobutyrate 28b according to protocol described for the compound 29a in Example 24 (Scheme 9). The ester 29b was isolated as colorless oil 96% yield (2.26 g). 1H NMR (400 MHz, CDCl3): δ 1.24 (3H, t, J=7.2 Hz); 2.07 (2H, m); 2.15 (2H, t, J=7.2 Hz)); 3.97 (2H, t, J=6.4 Hz); 4.10 (2H, q, J=7.2 Hz); 4.59 (2H, s); 6.88 (1H, s); 6.87 (1H, s); 7.24-7.27 (2H, m).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[C:9]1([Si:15]2(CCCC=C)[CH2:20][CH2:19][CH:18]([C:21]3[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=3)[CH2:17][CH2:16]2)C=[CH:13][CH:12]=[CH:11][CH:10]=1>>[CH2:9]([Si@H:15]1[CH2:16][CH2:17][C@H:18]([C:21]2[CH:29]=[CH:28][C:24]([C:25]([O:8][C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[O:26])=[CH:23][CH:22]=2)[CH2:19][CH2:20]1)[CH2:10][CH2:11][CH:12]=[CH2:13]
Reactant: Oc1ccc(Cl)cc1
Reactant: C=CCCC[Si]1(c2ccccc2)CCC(c2ccc(C(=O)O)cc2)CC1
Product: C=CCCC[Si@H]1CC[C@H](c2ccc(C(=O)Oc3ccc(Cl)cc3)cc2)CC1

Procedure:
The general procedure of Example 3 was repeated using 4-chlorophenol and 4-(4-phenyl-4-(4-pentenyl)-4-silacyclohexyl)benzoic acid, thereby obtaining the intended product.
Reaction SMILES: [OH:1][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6](Br)=[CH:5][CH:4]=1.[C:14]([O:18][C:19]([N:21]1[CH2:27][C@H:26]([O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[CH2:25][C@H:22]1[CH:23]=[O:24])=[O:20])([CH3:17])([CH3:16])[CH3:15].[Cl-].[NH4+]>O1CCCC1>[C:14]([O:18][C:19]([N:21]1[CH2:27][C@H:26]([O:28][Si:29]([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30])[CH2:25][C@H:22]1[CH:23]([OH:24])[C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]([CH2:2][OH:1])=[CH:4][CH:5]=1)=[O:20])([CH3:17])([CH3:16])[CH3:15]
Reactant: CC(C)(C)OC(=O)N1C[C@H](O[Si](C)(C)C(C)(C)C)C[C@H]1C=O
Reactant: OCc1ccc(Br)c2ccccc12
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1C[C@H](O[Si](C)(C)C(C)(C)C)C[C@H]1C(O)c1ccc(CO)c2ccccc12
Temperature: -72 °C
Reaction time: 0.5 h
Yield: 43.8 %

Procedure:
A solution of 4-hydroxymethyl-1-bromonaphthalene (3 g, 12.7 mmol) in tetrahydrofuran (50 ml) was added dropwise to a solution of 1.6M butyl lithium-hexane solution (20.6 ml, 32.9 mmol) in tetrahydrofuran (100 ml) at -72° C. in a nitrogen stream over 30 minutes. The resulting reaction solution was stirred at -72° C. for 30 minutes and a solution of (2S,4R)-N-t-butoxycarbonyl-4-(t-butyldimethylsiloxy)prolinal (4.17 g, 12.7 mmol) in tetrahydrofuran (50 ml) was added dropwise over 10 minutes. Then, the reaction solution was stirred at -63° C. for 10 minutes. After addition of saturated aqueous ammonium chloride, the reaction solution was concentrated in vacuo. The resulting residue was poured into a liquid mixture of ethyl acetate with water. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated in vacuo. The resulting oily residue was subjected to silica gel column chromatography (Wakogel™ C-300 heptane-ethyl acetate 3:1→2:1) to give (2S,4R)-N-t-butoxycarbonyl-4-t-butyldimethylsiloxy-2-[hydroxy(4-hydroxymethyl-1-naphthyl)methyl]pyrrolidine (2.71 g, yield: 44.0%) as a colorless oily substance.
Reaction SMILES: [CH2:1]([O:3][CH2:4][CH2:5][N:6]1[C:10]([C:11]([NH2:13])=[O:12])=[C:9]([N+:14]([O-])=O)[C:8]([CH2:17][CH3:18])=[N:7]1)[CH3:2].C([O-])=O.[NH4+]>C(O)C.[OH-].[Pd+2].[OH-]>[NH2:14][C:9]1[C:8]([CH2:17][CH3:18])=[N:7][N:6]([CH2:5][CH2:4][O:3][CH2:1][CH3:2])[C:10]=1[C:11]([NH2:13])=[O:12]
Reactant: CCOCCn1nc(CC)c([N+](=O)[O-])c1C(N)=O
Agent: [Pd+2]
Agent: O=C[O-]
Agent: [NH4+]
Solvent: CCO
Product: CCOCCn1nc(CC)c(N)c1C(N)=O
Yield: 49.2 %

Procedure:
A mixture of 1-(2-ethoxyethyl)-3-ethyl-4-nitro-1H-pyrazole-5-carboxamide from step 1 (5.70 g, 22 mmol) and palladium hydroxide (1.0 g) in ethanol (110 mL) was treated with ammonium formate (7.01 g, 111 mmol) in four unequal portions at about 10 minute intervals. The resulting mixture was heated under reflux for two hours and then cooled. The mixture was filtered through celite and concentrated. The resulting residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane as the eluent to provide 2.45 g of the title compound. 1H NMR (400 MHz, CDCl3): δ 1.17 (t, 3 H), 1.21-1.32 (m, 3 H), 2.60 (q, 2 H), 3.53 (q, 2 H), 3.79-3.95 (m, 2 H), 4.38-4.52 (m, 2 H). MS (ESI) m/z 227.
Reaction SMILES: C([O:8][CH2:9][C@@H:10]([O:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][O:21]1)[C@@:11]([O:17][CH3:18])([CH3:16])[CH2:12][CH2:13][CH:14]=[CH2:15])C1C=CC=CC=1.[H][H]>CO.[OH-].[OH-].[Pd+2]>[O:21]1[CH2:22][CH2:23][CH2:24][CH2:25][CH:20]1[O:19][C@@H:10]([C@@:11]([O:17][CH3:18])([CH3:16])[CH2:12][CH2:13][CH2:14][CH3:15])[CH2:9][OH:8]
Reactant: [H][H]
Reactant: C=CCC[C@@](C)(OC)[C@@H](COCc1ccccc1)OC1CCCCO1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: CCCC[C@@](C)(OC)[C@@H](CO)OC1CCCCO1

Procedure:
A mixture of (2R,3R)l-benzyloxy-2-tetrahydro-pyranyloxy-3-methoxy-3-methyl-6-heptene (1.78 mmol, 620 mg) and Pd(OH)2 on carbon (60 mg) in methanol (8 ml) is stirred 3 h under an hydrogen atmosphere whereby 82 ml of hydrogen is absorbed. The catalyst is filtered, washed with methanol and the methanol is removed in vacuo. The alcohol 12b is used as such in the next reaction.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([CH3:26])([C:10](=O)[CH2:11][NH:12][C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([F:22])=[C:18]([O:23][CH3:24])[CH:17]=2)=[S:14])[CH3:9])[CH:5]=[CH:4][C:3]=1[S:27]([NH2:30])(=[O:29])=[O:28]>CC(O)=O>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([C:10]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[C:18]([O:23][CH3:24])[CH:17]=3)[C:13]([SH:14])=[N:12][CH:11]=2)([CH3:26])[CH3:9])[CH:5]=[CH:4][C:3]=1[S:27]([NH2:30])(=[O:29])=[O:28]
Reactant: COc1cc(NC(=S)NCC(=O)C(C)(C)c2ccc(S(N)(=O)=O)c(Cl)c2)ccc1F
Solvent: CC(=O)O
Product: COc1cc(-n2c(C(C)(C)c3ccc(S(N)(=O)=O)c(Cl)c3)cnc2S)ccc1F
Temperature: 25 °C
Yield: 82.4 %

Procedure:
A solution of 2-chloro-4-(4-(3-(4-fluoro-3-methoxyphenyl)thioureido)-2-methyl-3-oxobutan-2-yl)benzenesulfonamide (8.6 g, 18.1 mmol) in AcOH (100 mL) was refluxed 3 h. After the reaction was complete, the solution was cooled to room temperature and azeotroped with toluene. The residue was triturated with Et2O, filtered and dried to provide the title compound (6.8 g, 82% yield) as a light yellow solid. 1H NMR (400 MHz, CDCl3+MeOD) δ 7.92 (d, J=8.4 Hz, 1H), 7.09 (s, 1H), 7.06 (d, J=8.4 Hz, 1H), 6.97 (t, J=8.4 Hz, 1H), 6.89 (s, 1H), 6.38 (m, 1H), 6.13 (d, J=7.2 Hz, 1H), 3.58 (s, 3H), 1.54 (s, 6H); MS (EI) m/z 456 (MH+).
Reaction SMILES: [CH3:1][C:2](=O)[C@@H:3]1[C@:20]2([CH3:21])[C@H:6]([C@H:7]3[C@H:17]([CH2:18][CH2:19]2)[C@:15]2([CH3:16])[C@H:10]([CH2:11][CH2:12][CH2:13][CH2:14]2)[CH2:9][CH2:8]3)[CH2:5][CH2:4]1.C(O)C.[NH2:26][OH:27].C([O-])(=O)C.[Na+]>ClCCl.O>[CH3:1][C:2](=[N:26][OH:27])[C@@H:3]1[C@:20]2([CH3:21])[C@H:6]([C@H:7]3[C@H:17]([CH2:18][CH2:19]2)[C@:15]2([CH3:16])[C@H:10]([CH2:11][CH2:12][CH2:13][CH2:14]2)[CH2:9][CH2:8]3)[CH2:5][CH2:4]1
Reactant: CC(=O)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4CCCC[C@]4(C)[C@H]3CC[C@]12C
Reactant: NO
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Solvent: CCO
Product: CC(=NO)[C@H]1CC[C@H]2[C@@H]3CC[C@H]4CCCC[C@]4(C)[C@H]3CC[C@]12C

Procedure:
3α-fluor, 5α-pregnan-20-one (10 mmol) is dissolved in dichloromethane 5 mL and ethanol 50 mL at rt and air atmosphere, in a 250 mL round bottom flask. 4 equiv. of NH2OH chlorhydrate and 4 equiv. of sodium acetate are dissolved in 5 mL H2O and then added to the steroid solution. 20 mL of ethanol are added and the mixture put on reflux overnight. The mixture is then cooled and the solvent removed under reduced pressure. The white residue is then treated with 50 mL H2O and 50 mL dichloromethane, the aqueous phase extracted with 3×30 mL dichloromethane. The collected organic phases are then dried over MgSO4, filtrated and the solvent removed under reduced pressure. The final residue is purified by silica flash column chromatography (dichloromethane:diethyl ether 4:1). Quantitative yield.
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][N:12]([CH:20]3[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][N:28]4[C:37]5[C:32](=[CH:33][CH:34]=[N:35][CH:36]=5)[CH:31]=[CH:30][C:29]4=[O:38])[CH2:22][CH2:21]3)C(=O)OC(C)(C)C)=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1.[ClH:39].C(OCC)(=O)C>>[ClH:39].[O:1]1[C:6]2[CH:7]=[CH:8][C:9]([CH2:11][NH:12][CH:20]3[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][N:28]4[C:37]5[C:32](=[CH:33][CH:34]=[N:35][CH:36]=5)[CH:31]=[CH:30][C:29]4=[O:38])[CH2:22][CH2:21]3)=[CH:10][C:5]=2[O:4][CH2:3][CH2:2]1
Reactant: CC(C)(C)OC(=O)N(Cc1ccc2c(c1)OCCO2)C1CCN(CCn2c(=O)ccc3ccncc32)CC1
Agent: Cl
Solvent: CCOC(C)=O
Product: O=c1ccc2ccncc2n1CCN1CCC(NCc2ccc3c(c2)OCCO3)CC1

Procedure:
To 0.15 g of tert-butyl (2,3-dihydro-1,4-benzodioxin-6-ylmethyl)(1-(2-(2-oxo-1,7-naphthyridin-1(2H)-yl)ethyl)piperidin-4-yl)carbamate, 8 mL of a 4 mol/L hydrogen chloride/ethyl acetate solution was added, the mixture was reacted at room temperature for 21 hours, and the solvent was distilled off under reduced pressure. Ethanol was added to the resultant residue, the solvent was distilled off under reduced pressure, ethyl acetate was then added to the resultant residue, and the solid was filtered off to obtain 0.15 g of 1-(2-(4-((2,3-dihydro-1,4-benzodioxin-6-ylmethyl)amino)piperidin-1-yl)ethyl)-1,7-naphthyridin-2(1H)-one hydrochloride as a yellow solid.
Reaction SMILES: Cl[C:2]1[C:11]2[CH:12]=[CH:13][S:14][C:10]=2[C:9]2[CH:8]=[CH:7][C:6]([C:15]([O-:17])=[O:16])=[CH:5][C:4]=2[N:3]=1.[NH2:18][CH2:19][C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1>CN1C(=O)CCC1.CO>[N:22]1[CH:23]=[CH:24][CH:25]=[C:20]([CH2:19][NH:18][C:2]2[C:11]3[CH:12]=[CH:13][S:14][C:10]=3[C:9]3[CH:8]=[CH:7][C:6]([C:15]([OH:17])=[O:16])=[CH:5][C:4]=3[N:3]=2)[CH:21]=1
Reactant: O=C([O-])c1ccc2c(c1)nc(Cl)c1ccsc12
Reactant: NCc1cccnc1
Solvent: CO
Solvent: CN1CCCC1=O
Product: O=C(O)c1ccc2c(c1)nc(NCc1cccnc1)c1ccsc12
Temperature: 120 °C
Reaction time: 17 h
Yield: 62 %

Procedure:
4-chlorothieno[3,2-c]quinoline-7-carboxylate (10 mg, 0.036 mmol) was suspended in NMP (0.1 ml) and 3-aminomethylpyridine (0.1 ml). The mixture was heated in a microwave oven at 120° C. for 10 nm. The reaction mixture was dissolved in a mixture of NMP and MeOH and the ester intermediate purified by preparative HPLC. After genevac evaporation of the solvents, the resulting solid was dissolved in a 1:1 mixture of THF and MeOH (0.6 ml). 5N aqueous LiOH (0.2 ml) was added and the mixture stirred at room temperature for 17 hrs. Water and aqueous HCl were added and the solution of 4-(pyridin-3-ylmethylamino)thieno[3,2-c]quinoline-7-carboxylic acid was purified by preparative HPLC. Removal of the solvents by genevac evaporation provided compound 4-(pyridin-3-ylmethylamino)thieno[3,2-c]quinoline-7-carboxylic acid as a white solid (10 mg, 62% yield). LCMS (ES): 95% pure, m/z 336 [M+1]+. 1H NMR (CDCl3, 400 MHz) δ 5.23 (s, 2H), 7.71-7.78 (m, 4H), 8.11 (d, J=5.6, 1H), 8.47 (d, J=8.0, 1H), 8.49 (d, J=0.8, 1H), 8.62 (d, J=5.2, 1H), 8.97 (s, 1H) ppm.
Reaction SMILES: C([N:5]1[C:12](=O)[N:11]2[C:7](=[N:8][C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=32)[S:6]1)CCC.[C:18](#N)C>>[CH3:18][C:12]1[N:11]2[C:7](=[N:8][C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=32)[S:6][N:5]=1
Reactant: CC#N
Reactant: CCCCn1sc2nc3ccccc3n2c1=O
Product: Cc1nsc2nc3ccccc3n12
Yield: 88 %

Procedure:
2-Butyl-1,2,4-thiadiazolo[4,5-a]benzimidazole-3(2H)-one (1.00 g, 4.04 mmol) was refluxed in 100 mL acetonitrile for 18 h. The solvent was then evaporated and the residue was recrystallized from methanol to give 0.671 g (88%) of the title compound: mp 192-193° C.; 1H NMR (CDCl3) δ 7.81 (dm, 2H), 7.47 (td, 1H), 7.34 (td, 1H), 2.92 (s, 3H) ppm; IR (KBr) ν 1564, 1481, 1453, 1430, 1304, 1208, 756, 745 cm-1 ; MS m/z 189 (M+), 148 (M+ --CH3CN)
Reaction SMILES: C(N1CCCC1=O)=C.[C:9]([O:14][CH2:15][CH2:16][CH2:17]CCCCCCCCC)(=[O:13])[C:10]([CH3:12])=[CH2:11].O=O.N(C(C)(C)C#N)=NC(C)(C)C#N>O>[C:9]([O:14][CH2:15][CH:16]=[CH2:17])(=[O:13])[C:10]([CH3:12])=[CH2:11]
Reactant: C=C(C)C(=O)OCCCCCCCCCCCC
Agent: C=CN1CCCC1=O
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Agent: *CC(*)C
Solvent: O
Product: C=CCOC(=O)C(=C)C

Procedure:
The dimer of allyl methacrylate, which was prepared according to Example 1, was added in the amount of 3 wt.-% (related to the entire mixture) to the mixture containing 80 wt.-% N-vinylpyrrolidone and 20 wt. % dodecyl methacrylate. The mixture was homogenized, freed of air oxygen and polymerized in the presence of 0.4 wt.-% azobisisobutyronitrile in a polypropylene mold at 60° C. for 16 h. The resulting gel contained, after swelling with water, 72 wt.-% water at G=0.027 MPa. The soluble portion was 2%.
Reaction SMILES: C([BH3-])#N.[Na+].[CH3:5][O:6][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[CH:14][CH:13]=[CH:12]2.Cl.[OH-].[NH4+]>CCO.O>[CH3:5][O:6][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[NH:15][CH2:14][CH2:13][CH2:12]2
Reactant: COc1cccc2cccnc12
Agent: Cl
Agent: [BH3-]C#N
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: COc1cccc2c1NCCC2
Temperature: 0 °C
Yield: 81.8 %

Procedure:
Add sodium cyanoborohydride (505 g, 8.11 mol) in EtOH (1 L) to a solution of 8-methoxy quinoline (425 g, 2.673 mol) in EtOH (9 L), and stir. Cool the reaction mixture to an internal temperature of 0° C. and add HCl (35%, 1.12 L, 10.962 mol) dropwise over 60 min so that the internal temperature did not rise above 20° C. Allow the reaction mixture to warm to ambient temperature and then heat to reflux for 2.5 hours. Cool to ambient temperature and stir overnight. Add ammonium hydroxide (25%, 1 L); dilute with water (15 L); and extract the mixture with dichloromethane (3×10 L). Combine the organic layers and dry over sodium sulfate. Remove the solids by filtration. Collect the filtrate and concentrate under reduced pressure to give a residue. Purify the residue by silica gel flash chromatography, eluting with ethyl acetate: hexane (1:10) to give the title compound (357 g, 82%). ESI (m/z) 164(M+H).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([C:13]([NH2:15])=[O:14])[C:8](=[O:16])[CH2:7]2)([O-])=O.[H][H]>[Pd].CN(C)C=O>[NH2:1][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([C:13]([NH2:15])=[O:14])[C:8](=[O:16])[CH2:7]2
Reactant: [H][H]
Reactant: NC(=O)N1C(=O)Cc2cc([N+](=O)[O-])ccc21
Agent: [Pd]
Solvent: CN(C)C=O
Product: NC(=O)N1C(=O)Cc2cc(N)ccc21

Procedure:
To a solution of 5.0 g. of 5-nitro-2-oxindole-1-carboxamide in 110 ml. of N,N-dimethylformamide was added 0.5 g. of 10% palladium-on-carbon, and the resulting mixture was shaken under an atmosphere of hydrogen at an initial pressure of 5 kg/cm2 until hydrogen uptake ceased. The catalyst was removed by filtration, and the filtrate was diluted with brine and extracted with ethyl acetate. The extracts were dried (MgSO4) and evaporated in vacuo to give a dark-colored oil which solidified after trituration under water. This afforded 3.0 g. of the title compound as a yellow solid, mp 189°-191° C.
Reaction SMILES: C(OC(=O)[NH:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][CH2:15][N:16]2[CH2:21][CH2:20][CH:19]([C:22](=[O:30])[C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[CH2:18][CH2:17]2)[CH2:10][CH2:9]1)(C)(C)C.[ClH:32].O1CCOCC1>ClCCl.C(OC(C)C)(C)C>[ClH:32].[NH2:7][C@H:8]1[CH2:13][CH2:12][C@H:11]([CH2:14][CH2:15][N:16]2[CH2:17][CH2:18][CH:19]([C:22]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)=[O:30])[CH2:20][CH2:21]2)[CH2:10][CH2:9]1
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@H](CCN2CCC(C(=O)c3ccc(F)cc3)CC2)CC1
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Solvent: CC(C)OC(C)C
Product: N[C@H]1CC[C@H](CCN2CCC(C(=O)c3ccc(F)cc3)CC2)CC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 100 %

Procedure:
Trans-(4-{2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-ethyl}-cyclohexyl)-carbamic acid tert-butyl ester (1.4 g, 3.24 mmol) was dissolved in 2 ml dichloromethane and 4N HCl in dioxane (9.7 ml, 38.8 mmol) was added. The white suspension was stirred for 4 hours at room temperature, diluted with diisopropylether and filtered. The crystals were washed with diisopropylether and dried for 2 hours at 50° C. and <20 mbar, to get the desired salt as a white solid (1.2 g, 100%) [MS: m/e=333.3 (M+H+)].
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([S:9]([O-:11])=[O:10])=[CH:5][CH:4]=1)#[N:2].[Na+].Br[C:14]1[CH:22]=[CH:21][C:20]2[N:19]([CH3:23])[C:18]3[CH2:24][CH:25]4[NH:29][CH:28]([C:17]=3[C:16]=2[C:15]=1[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:27][CH2:26]4>>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([S:9]([C:14]2[CH:22]=[CH:21][C:20]3[N:19]([CH3:23])[C:18]4[CH2:24][CH:25]5[NH:29][CH:28]([C:17]=4[C:16]=3[C:15]=2[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[CH2:27][CH2:26]5)(=[O:11])=[O:10])=[CH:7][CH:8]=1)#[N:2]
Reactant: N#Cc1ccc(S(=O)[O-])cc1
Reactant: Cn1c2c(c3c(C(=O)OC(C)(C)C)c(Br)ccc31)C1CCC(C2)N1
Agent: [Na+]
Product: Cn1c2c(c3c(C(=O)OC(C)(C)C)c(S(=O)(=O)c4ccc(C#N)cc4)ccc31)C1CCC(C2)N1
Yield: 50 %

Procedure:
Intermediate 11 was coupled with the product of Example 27, step B following the procedure of Example 27, step C. The crude product was purified by flash column chromatography (SiO2, 8:2 hexane/ethyl acetate) to give tert-butyl 2-(4-cyanophenyl)sulfonyl-5-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole-carboxylate (184 mg, 50%) as a yellow solid: 1H NMR (CDCl3, 300 MHz) δ 8.18 (s, 1H), 8.05 (dd, J=6.9, 1.5 Hz, 2H), 7.75 (dd, J=6.9, 1.5 Hz, 2H), 7.66 (dd, J=8.7, 1.5 Hz, 1H), 7.33 (d, J=8.7 Hz, 1H), 5.26 (br s, 1H), 4.69 (br s, 1H), 3.62 (s, 3H), 3.37 (br s, 1H), 2.51 (d, J=15.9 Hz, 1H), 2.13-2.41 (m, 2H), 1.87-1.99 (m, 1H), 1.67-1.70 (m, 1H), 1.39 (br s, 9H).