Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.Cl.[F:3][C:4]1[CH:5]=[CH:6][C:7]2[N:11]=[C:10]([C@@H:12]([NH2:14])[CH3:13])[N:9]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:8]=2[CH:21]=1.Cl[C:23]1[C:24](=[O:31])[N:25]([CH3:30])[N:26]=[CH:27][C:28]=1[Cl:29].C(N(C(C)C)CC)(C)C>C(O)(C)C.CCOC(C)=O>[Cl:29][C:28]1[CH:27]=[N:26][N:25]([CH3:30])[C:24](=[O:31])[C:23]=1[NH:14][C@H:12]([C:10]1[N:9]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:8]2[CH:21]=[C:4]([F:3])[CH:5]=[CH:6][C:7]=2[N:11]=1)[CH3:13]
Reactant: C[C@H](N)c1nc2ccc(F)cc2n1-c1ccccc1
Reactant: Cn1ncc(Cl)c(Cl)c1=O
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CC(C)O
Solvent: CCN(C(C)C)C(C)C
Product: C[C@H](Nc1c(Cl)cnn(C)c1=O)c1nc2ccc(F)cc2n1-c1ccccc1
Reaction time: 20 h
Yield: 6.4 %

Procedure:
(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine dihydrochloride (1.0 g, 3.05 mmol), 4,5-dichloro-2-methyl-2H-pyridazin-3-one (J. Org. Chem. 2473-76, 46, 1981) (0.546 g, 3.05 mmol) and diisopropylethylamine (2.1 mL, 12.8 mmol) in isopropanol (5 mL) was heated to reflux for 4.25 h then at 75° C. for 20 h. The reaction mixture was cooled, diluted with EtOAc (20 mL) and washed with 1M sodium carbonate (10 mL). The organic extracts were dried (Na2SO4), evaporated to dryness and purified by column chromatography (Si—PCC, gradient 0-10% MeOH in DCM then gradient 20-100% EtOAc in DCM). Fractions containing the less polar product were evaporated and freeze dried to give 323 as a yellow solid, (78 mg, 6.4%). LCMS (Method C): RT 4.80 min [M+H]+ 398.00. 1H NMR δ (ppm) (DMSO-d): 7.77 (1H, dd, J=8.82, 4.85 Hz), 7.56-7.55 (6H, m), 7.14 (1H, ddd, J=9.9, 8.9, 2.50 Hz), 6.89 (1H, dd, J=8.91, 2.51 Hz), 6.61 (1H, d, J=9.09 Hz), 5.94 (1H, t, J=7.66 Hz), 3.56 (3H, s), 1.51 (3H, d, J=6.65 Hz)
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]([C:18](=[O:20])[CH3:19])=[C:11]3[CH:12]=[CH:13][CH:14]=[C:15](Cl)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[NH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1>>[Br:1][C:2]1[CH:3]=[C:4]([C:8]2[C:17]([C:18](=[O:20])[CH3:19])=[C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([N:21]4[CH2:25][CH2:24][CH2:23][CH2:22]4)[N:10]3[N:9]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: C1CCNC1
Reactant: CC(=O)c1c(-c2cccc(Br)c2)nn2c(Cl)cccc12
Product: CC(=O)c1c(-c2cccc(Br)c2)nn2c(N3CCCC3)cccc12
Yield: 96 %

Procedure:
In a similar manner as described in Example 1 from 1-[2-(3-bromophenyl)-7-chloropyrazolo[1,5-a]pyridin-3-yl]ethanone (3.00 g, 8.6 mmol) and pyrrolidine, 1-[2-(3-bromophenyl)-7-(1-pyrrolidinyl)pyrazolo[1,5-a]pyridin-3-yl]ethanone (3.18 g, 96%) was obtained as a yellow syrup. 1H NMR (CDCl3): δ 7.78–7.74 (m, 2H), 7.56 (d, 1H), 7.50 (d, 1H), 7.38–7.28 (m, 2H), 6.14 (d, 1H), 3.72 (m, 4H), 2.12 (s, 3H), 1.98 (m, 4H); MS m/z 384 (M+1).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[C:10]([Cl:16])[CH:9]=2)[CH:5]=[N:6][CH:7]=1.[F:17][C:18]([F:25])([F:24])[CH2:19][S:20](Cl)(=[O:22])=[O:21]>N1C=CC=CC=1>[Cl:16][C:10]1[CH:9]=[C:8]([C:4]2[CH:3]=[C:2]([NH:1][S:20]([CH2:19][C:18]([F:25])([F:24])[F:17])(=[O:22])=[O:21])[CH:7]=[N:6][CH:5]=2)[CH:15]=[CH:14][C:11]=1[C:12]#[N:13]
Reactant: O=S(=O)(Cl)CC(F)(F)F
Reactant: N#Cc1ccc(-c2cncc(N)c2)cc1Cl
Solvent: c1ccncc1
Product: N#Cc1ccc(-c2cncc(NS(=O)(=O)CC(F)(F)F)c2)cc1Cl
Yield: 27.5 %

Procedure:
According to General Sulfonylation Procedure 2 in Example 1, to a solution of 4-(5-amino-pyridin-3-yl)-2-chloro-benzonitrile (20 mg, 87 μmol, 1 eq) in anhydrous pyridine (500 μl) was added 2,2,2-trifluoro-ethanesulfonyl chloride (10.6 μl, 96 μmol, 1.1 eq). The product was purified by preparative TLC, the plate was eluted with dichloromethane/methanol 95/5, to give N-(5-(3-chloro-4-cyanophenyl)pyridin-3-yl)-2,2,2-trifluoroethanesulfonamide (9 mg, >95% purity, yield: 27.6%). The isolated product was lyophilized and identified by LC-MS (system 1) and NMR (system 3): ESI-MS m/z: 376 [M+H]+, retention time=2.10 min, 1H NMR (500 MHz, DMSO-d6) δ ppm 4.75 (q, J=9.66 Hz, 2H) 7.87-7.91 (m, 2H) 8.11-8.14 (m, 1H) 8.14 (s, 1H) 8.46 (d, J=2.44 Hz, 1H) 8.74 (d, J=1.83 Hz, 1H) 10.94 (br. s., 1H).
Reaction SMILES: [CH:1]1([CH:6]2[CH2:15][CH2:14][C:13]3[C:8](=[C:9]([Cl:19])[C:10]([Cl:18])=[C:11]([O:16]C)[CH:12]=3)[C:7]2=[O:20])[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.N1C=CC=CC=1>O>[CH:1]1([CH:6]2[CH2:15][CH2:14][C:13]3[C:8](=[C:9]([Cl:19])[C:10]([Cl:18])=[C:11]([OH:16])[CH:12]=3)[C:7]2=[O:20])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: COc1cc2c(c(Cl)c1Cl)C(=O)C(C1CCCC1)CC2
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: O=C1c2c(cc(O)c(Cl)c2Cl)CCC1C1CCCC1
Temperature: 180 °C

Procedure:
2-Cyclopentyl-6-methoxy-7,8-dichloro-1-tetralone (6.58 g., 0.02 mole) is mixed with pyridine hydrochloride (60 g.) and the mixture is heated at 180° C. for one hour. The mixture is poured into water (ca. 400 ml.). The solid that separates is collected, washed with water and air dried to obtain 2-cyclopentyl-6-hydroxy-7,8-dichloro-1-tetralone.
Reaction SMILES: [NH2:1][C:2]1[CH:28]=[CH:27][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[O:19][C:18]([C:20]([NH:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=[CH:17][CH:16]=3)[CH2:10][CH2:9]2)=[O:7])=[CH:4][C:3]=1[F:29].Cl[C:31](OC1C=CC([N+]([O-])=O)=CC=1)=[O:32].[CH:43]1([NH2:47])[CH2:46][CH2:45][CH2:44]1>ClCCl.O>[C:23]([NH:22][C:20]([C:18]1[O:19][C:15]([CH2:14][N:11]2[CH2:10][CH2:9][N:8]([C:6](=[O:7])[C:5]3[CH:27]=[CH:28][C:2]([NH:1][C:31]([NH:47][CH:43]4[CH2:46][CH2:45][CH2:44]4)=[O:32])=[C:3]([F:29])[CH:4]=3)[CH2:13][CH2:12]2)=[CH:16][CH:17]=1)=[O:21])([CH3:26])([CH3:24])[CH3:25]
Reactant: NC1CCC1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: CC(C)(C)NC(=O)c1ccc(CN2CCN(C(=O)c3ccc(N)c(F)c3)CC2)o1
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)NC(=O)c1ccc(CN2CCN(C(=O)c3ccc(NC(=O)NC4CCC4)c(F)c3)CC2)o1
Reaction time: 0.5 h
Yield: 8.4 %

Procedure:
5-((4-(4-amino-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylfuran-2-carboxamide (113 mg, 0.280 mmol) and 4-nitrophenol chloroformate (56 mg, 0.238 mmol) were combined and stirred in dichloromethane for 1 hour at room temperature. Cyclobutylamine (59.6 mg, 0.839 mmol, 71.6 μl) was added and the reaction was stirred for 30 minutes. The reaction mixture was diluted with water and flushed through a hydrophobic frit. The organic phase was concentrated under vacuum and purified by acidic reverse phase HPLC to afford the title compound (10 mg). MS (ESI) m/z 500.3 [M+H]+
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([C:9]2[O:13][C:12](=[O:14])[N:11]([C:15]3[CH:24]=[CH:23][C:18]([C:19]([O:21]C)=[O:20])=[CH:17][CH:16]=3)[N:10]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2].B(Br)(Br)Br>ClCCl>[C:1]([C:3]1[CH:4]=[C:5]([C:9]2[O:13][C:12](=[O:14])[N:11]([C:15]3[CH:24]=[CH:23][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=3)[N:10]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2]
Reactant: COC(=O)c1ccc(-n2nc(-c3cccc(C#N)c3)oc2=O)cc1
Agent: BrB(Br)Br
Solvent: ClCCl
Product: N#Cc1cccc(-c2nn(-c3ccc(C(=O)O)cc3)c(=O)o2)c1
Yield: 80.1 %

Procedure:
Methyl 4-[5-(3-cyanophenyl)-2-oxo-1,3,4-oxadiazol-3(2H)-yl]benzoate (0.60 g, 1.87 mmol) is then treated with boron tribromide (1M in dichloromethane, 5.6 mL, 5.6 mmol) in dichloromethane (20 mL) at room temperature overnight. The volatiles are removed in vacuum and the residue is treated with water. The crude product is separated by column chromatography (silica gel, 1:9 methanol-dichloromethane) to furnish the desired product, 4-[5-(3-cyanophenyl)-2-oxo-1,3,4-oxadiazol-3(2H)-yl]benzoic acid (0.46 g, 81%). m.p. 294-295° C. (decomp.). 1H NMR (CDCl3, 300 MHz) δ (ppm) 7.47 (t, 1H), 7.77 (d, 2H), 7.88-8.00 (m, 4H). (ES+) m/z: 307.
Reaction SMILES: [NH:1]([C:3]1[C:8]([F:9])=[CH:7][C:6]([F:10])=[CH:5][N:4]=1)N>CO.[Ni]>[NH2:1][C:3]1[C:8]([F:9])=[CH:7][C:6]([F:10])=[CH:5][N:4]=1
Reactant: NNc1ncc(F)cc1F
Agent: [Ni]
Solvent: CO
Product: Nc1ncc(F)cc1F
Reaction time: 24 h
Yield: 83.1 %

Procedure:
Charged in a hydrogenation reactor were 500 ml of methanol, 14.5 g of the compound obtained in Step 4 and 11.5 g of Raney nickel as a catalyst, and H2 gas was introduced therein. The reactor was kept at room temperature for 24 hours, and the reaction mixture was filtered through Cellite® to remove the catalyst. The resulting solution was concentrated under a reduced pressure to obtain 10.8 g of the title compound as a light yellow solid (purity: 98.0%).
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:8]([N+:27]([O-:29])=[O:28])=[CH:9][C:10]2[O:14][C:13]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)=[C:12]([C:22](=[O:25])[NH:23][CH3:24])[C:11]=2[CH:26]=1)(=O)=O.[CH3:32][O:33][C:34]1[CH:43]=[CH:42][C:41](B2OC(C)(C)C(C)(C)O2)=[CH:40][C:35]=1[C:36]([O:38][CH3:39])=[O:37].C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1>[F:21][C:18]1[CH:19]=[CH:20][C:15]([C:13]2[O:14][C:10]3[CH:9]=[C:8]([N+:27]([O-:29])=[O:28])[C:7]([C:41]4[CH:42]=[CH:43][C:34]([O:33][CH3:32])=[C:35]([CH:40]=4)[C:36]([O:38][CH3:39])=[O:37])=[CH:26][C:11]=3[C:12]=2[C:22](=[O:25])[NH:23][CH3:24])=[CH:16][CH:17]=1
Reactant: COC(=O)c1cc(B2OC(C)(C)C(C)(C)O2)ccc1OC
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc([N+](=O)[O-])c(OS(=O)(=O)C(F)(F)F)cc12
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1COCCO1
Solvent: O
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc([N+](=O)[O-])c(-c3ccc(OC)c(C(=O)OC)c3)cc12
Temperature: 100 °C

Procedure:
To a mixture of 2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-nitrobenzofuran-5-yl trifluoromethanesulfonate (750 mg, 1.622 mmol), methyl 2-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (569 mg, 1.947 mmol) and cesium carbonate (1057 mg, 3.24 mmol) in dioxane (20 mL)/water (1.0 mL) at rt under nitrogen was added Pd(PPh3)4(0) (187 mg, 0.162 mmol). The reaction mixture was heated to 100° C. and maintained at the same temperature for overnight. The reaction mixture was filtered through celite, and the celite bed washed with ethyl acetate. The filtrate was concentrated and the residue purified by Combiflash using MeOH/CHCl3 as eluant. The desired fraction was collected at 2.5% MeOH in CHCl3. Yield: 0.650 g (83%).
Reaction SMILES: C(OC([N:8]([CH2:13][CH2:14][CH2:15][N:16]1[C:20]([C:21]2[CH:26]=[CH:25][C:24]([N:27]3[CH2:32][CH2:31][O:30][CH2:29][CH2:28]3)=[CH:23][CH:22]=2)=[CH:19][S:18][C:17]1=[N:33][C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)[CH2:9][C:10]([OH:12])=[O:11])=O)(C)(C)C.Cl>>[F:40][C:37]1[CH:36]=[CH:35][C:34]([N:33]=[C:17]2[N:16]([CH2:15][CH2:14][CH2:13][NH:8][CH2:9][C:10]([OH:12])=[O:11])[C:20]([C:21]3[CH:26]=[CH:25][C:24]([N:27]4[CH2:28][CH2:29][O:30][CH2:31][CH2:32]4)=[CH:23][CH:22]=3)=[CH:19][S:18]2)=[CH:39][CH:38]=1
Reactant: CC(C)(C)OC(=O)N(CCCn1c(-c2ccc(N3CCOCC3)cc2)csc1=Nc1ccc(F)cc1)CC(=O)O
Agent: Cl
Product: O=C(O)CNCCCn1c(-c2ccc(N3CCOCC3)cc2)csc1=Nc1ccc(F)cc1

Procedure:
The compound (30 mg) obtained in the above (2) was treated in a similar manner to in Example 9 (2) to give the title compound (31 mg) as hydrochloride.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:7]([C:10]1[CH:11]=[N:12][C:13]([N:16]2[CH2:21][CH2:20][CH:19]([C:22]3[C:31]([CH:32]([F:43])[C:33]4[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][CH:34]=4)=[C:30]([CH:44]4[CH2:49][CH2:48][C:47]([F:51])([F:50])[CH2:46][CH2:45]4)[C:29]4[CH:28]([O:52]CC5C=CC(OC)=CC=5)[CH2:27][C:26]([CH3:63])([CH3:62])[CH2:25][C:24]=4[N:23]=3)[CH2:18][CH2:17]2)=[N:14][CH:15]=1)(O)=[O:8]>>[F:51][C:47]1([F:50])[CH2:46][CH2:45][CH:44]([C:30]2[C:29]3[CH:28]([OH:52])[CH2:27][C:26]([CH3:62])([CH3:63])[CH2:25][C:24]=3[N:23]=[C:22]([CH:19]3[CH2:18][CH2:17][N:16]([C:13]4[N:14]=[CH:15][C:10]([C:7]([N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)=[O:8])=[CH:11][N:12]=4)[CH2:21][CH2:20]3)[C:31]=2[CH:32]([F:43])[C:33]2[CH:34]=[CH:35][C:36]([C:39]([F:40])([F:42])[F:41])=[CH:37][CH:38]=2)[CH2:49][CH2:48]1
Reactant: COc1ccc(COC2CC(C)(C)Cc3nc(C4CCN(c5ncc(C(=O)O)cn5)CC4)c(C(F)c4ccc(C(F)(F)F)cc4)c(C4CCC(F)(F)CC4)c32)cc1
Reactant: C1COCCN1
Product: CC1(C)Cc2nc(C3CCN(c4ncc(C(=O)N5CCOCC5)cn4)CC3)c(C(F)c3ccc(C(F)(F)F)cc3)c(C3CCC(F)(F)CC3)c2C(O)C1

Procedure:
Reactions similar to those of the second step of Reference Example 25 and Example 38 were performed except for using morpholine instead of methylamine aqueous solution, and from 70 mg of the crude product of 2-[1-(5-Carboxypyrimidin-2-yl)piperidin-4-yl]-4-(4,4-difluorocyclohexyl)-3-{fluoro[4-(trifluoromethyl)phenyl]methyl}-5-[(4-methoxybenzyl)oxy]-7,7-dimethyl-5,6,7,8-tetrahydroquinoline, which was prepared in the first step of Reference Example 25, 27 mg of the title compound was obtained as a white solid (yield: 49%).
Reaction SMILES: [CH2:1]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[NH2:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.O.[C:21](O)(=[O:25])[C:22](O)=[O:23]>Cl>[CH2:1]([N:8]1[C:9]2[C:10](=[CH:11][C:12]([N+:15]([O-:17])=[O:16])=[CH:13][CH:14]=2)[NH:18][C:22](=[O:23])[C:21]1=[O:25])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1cc([N+](=O)[O-])ccc1NCc1ccccc1
Reactant: O=C(O)C(=O)O
Agent: Cl
Solvent: O
Product: O=c1[nH]c2cc([N+](=O)[O-])ccc2n(Cc2ccccc2)c1=O
Temperature: 25 °C
Yield: 48.1 %

Procedure:
A mixture of 0,5 g (2.1 mmol) N-benzyl-2-amino-4-nitroaniline and 0,55 g (4,4 mmol) oxalic acid dihydrate in 30 ml 4N hydrochloric acid was refluxed for 5 h. After cooling to 25° C. the product was filtered off and washed with water. The crude product was recrystallized (dimethylformamidewater), washed with 10 ml water, 5 ml ethanol and 5 ml ether to give 0.3 g (49%) 1-benzyl-6-nitroquinoxaline-2,3(1H,4H)-dione. M.p. (DSC): 292.2 ° C. 1H-NMR (DMSO-d6): 12.4 (H, broad s), 8.2-7.0 (8H, m), 5.4 (2H, s).
Reaction SMILES: [OH-].[K+].[C:3]([C:7]1[CH:8]=[C:9]([CH3:12])[CH2:10][CH:11]=1)([CH3:6])([CH3:5])[CH3:4].[C:13]([C:17]1[CH:34]=[CH:33][C:20]([C:21]([C:23]2[CH:28]=[CH:27][C:26]([C:29]([CH3:32])([CH3:31])[CH3:30])=[CH:25][CH:24]=2)=O)=[CH:19][CH:18]=1)([CH3:16])([CH3:15])[CH3:14].Cl>C(OCC)C.C(COC)OC>[C:3]([C:7]1[CH:8]=[C:9]([CH3:12])[C:10](=[C:21]([C:23]2[CH:28]=[CH:27][C:26]([C:29]([CH3:31])([CH3:30])[CH3:32])=[CH:25][CH:24]=2)[C:20]2[CH:33]=[CH:34][C:17]([C:13]([CH3:15])([CH3:14])[CH3:16])=[CH:18][CH:19]=2)[CH:11]=1)([CH3:6])([CH3:5])[CH3:4]
Reactant: CC1=CC(C(C)(C)C)=CC1
Reactant: CC(C)(C)c1ccc(C(=O)c2ccc(C(C)(C)C)cc2)cc1
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CCOCC
Solvent: COCCOC
Product: CC1=CC(C(C)(C)C)=CC1=C(c1ccc(C(C)(C)C)cc1)c1ccc(C(C)(C)C)cc1

Procedure:
In a 200 ml three-necked flask equipped with a magnetic stirrer chip and three-way cock thoroughly purged with nitrogen, 1.58 g of powdery potassium hydroxide (28.2 mmol) and 100 ml of dehydrated dimethoxy ethane were added in a nitrogen atmosphere. To the suspension, 2.31 g of 3-tert-butyl-1-methyl-cyclopentadiene (17.0 mmol) was gradually added dropwise at room temperature and stirred under reflux for 1 hr. Thereafter, a solution prepared by dissolving 5.25 g of 4,4′-di-tert-butyl-benzophenone (17.8 mmol) to 40 ml of dehydrated dimethoxyethane was gradually added dropwise and stirred under reflux for 2 days. To the resulting reaction mixture, 50 ml of a hydrochloric acid aqueous solution (1N) was gradually added dropwise in an ice bath and stirred at room temperature for some time. Diethyl ether was added to the mixed solution to separate an organic phase. The organic phase was washed with a saturated sodium bicarbonate aqueous solution, water and saturated brine. The organic phase was dried with anhydrous magnesium sulfate, thereafter the drying agent was filtered off and the solvent was distilled off from the filtrate under reduced pressure to give a reddish-brown solid. The solid was purified with a column chromatography using 240 g of silica gel (developing solvent: n-hexane) and the developing solvent was distilled off under reduced pressure, and thereby the aimed compound was obtained in an amount of 2.10 g (5.09 mmol) as a reddish-orange solid (yield: 30%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=[O:13].[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1>>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([S:22]([NH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=[O:13])(=[O:24])=[O:23])=[CH:18][CH:17]=1
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Reactant: NCCCCCCCCCCC(=O)O
Product: O=C(O)CCCCCCCCCCNS(=O)(=O)c1ccc(Cl)cc1

Procedure:
11-Aminoundecanoic acid (4.02 g, 0.02 mol) was treated with 4-chlorobenzenesulphonyl chloride (4.22 g, 0.02 mol) as described in Example 4 to give the title compound which was recrystallised from 2-propanol/ether (1.8 g, m.p. 128°-9° C.).
Reaction SMILES: C([O:5][C:6](=[O:21])[CH:7]=[CH:8][C:9]1[CH:20]=[N:19][C:12]2[NH:13][CH2:14][C:15](=[O:18])[NH:16][CH2:17][C:11]=2[CH:10]=1)(C)(C)C.C(Cl)Cl.C(O)(C(F)(F)F)=O>>[O:18]=[C:15]1[CH2:14][NH:13][C:12]2[N:19]=[CH:20][C:9]([CH:8]=[CH:7][C:6]([OH:21])=[O:5])=[CH:10][C:11]=2[CH2:17][NH:16]1
Reactant: CC(C)(C)OC(=O)C=Cc1cnc2c(c1)CNC(=O)CN2
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: O=C(O)C=Cc1cnc2c(c1)CNC(=O)CN2
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 60.9 %

Procedure:
3-(3-Oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl)-acrylic acid tert-butyl ester (96 mg, 0.31 mmol) was dissolved into 1:1 CH2Cl2/TFA (2 mL) and stirred at room temperature for 30 min. The solvents were removed in vacuo to afford the title compound as a brown solid (44 mg, 61%) and as a mixture of amide rotomers. 1H NMR (300 MHz, DMSO-d6). 8.18 (t, J=5.7 Hz, 1H), 8.07 (d, J=2.1 Hz, 1H), 7.37 (d, J=15.8 Hz, 1H), 7.35 (t, J=5.3 Hz, 1H), 6.24 (d, J=15.8 Hz, 1H), 4.28 (d, J=5.7 Hz, 2H), 3:98 (d, J=5.1 Hz, 2H), 1.45 (s, 9H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:12])[CH2:9][NH:10][CH3:11])=[CH:4][CH:3]=1.[Br:13][C:14]1[S:18][C:17]2[C:19](=[O:23])[CH2:20][CH2:21][CH2:22][C:16]=2[C:15]=1[S:24](Cl)(=[O:26])=[O:25]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([OH:12])[CH2:9][N:10]([CH3:11])[S:24]([C:15]2[C:16]3[CH2:22][CH2:21][CH2:20][C:19](=[O:23])[C:17]=3[S:18][C:14]=2[Br:13])(=[O:26])=[O:25])=[CH:6][CH:7]=1
Reactant: O=C1CCCc2c1sc(Br)c2S(=O)(=O)Cl
Reactant: CNCC(O)c1ccc(F)cc1
Product: CN(CC(O)c1ccc(F)cc1)S(=O)(=O)c1c(Br)sc2c1CCCC2=O

Procedure:
From 1-(4-fluorophenyl)-2-methylamino-ethanol (the compound of Preparation Example 17) (186 mg) and 2-bromo-7-oxo-4,5,6,7-tetrahydro-benzo[b]thiophene-3-sulfonyl chloride (the compound of Preparation Example 9) (330 mg), the title compound (373 mg) was obtained as a light brown candy-like substance, in the same way as Preparation Example 41.
Reaction SMILES: Cl.[CH2:2]([CH:5]1C=CC=C[O:6]1)[C:3]#C.[CH3:11][C:12]12[C:18]([CH3:20])([CH3:19])[CH:15]([CH2:16][CH2:17]1)[CH2:14][C:13]2=O.[N:22]1C=CC=CC=1>C(O)C>[CH2:5]([O:6][N:22]=[C:13]1[CH2:14][CH:15]2[C:18]([CH3:20])([CH3:19])[C:12]1([CH3:11])[CH2:17][CH2:16]2)[C:2]#[CH:3]
Reactant: CC12CCC(CC1=O)C2(C)C
Reactant: C#CCC1C=CC=CO1
Reactant: c1ccncc1
Agent: Cl
Solvent: CCO
Product: C#CCON=C1CC2CCC1(C)C2(C)C
Reaction time: 3 h
Yield: 74 %

Procedure:
59.0 g (0.55 mole) of propargyloxamine hydrochloride are added to a solution of 76 g (0.5 mole) of (±)-1,7,7-trimethyl-bicyclo[2,2,1]heptane-2-one in 225 ml of pyridine and 450 ml of dry ethanol. The reaction mixture is boiled for 3 hours and then it is evaporated in vacuo. The residue is diluted with water, and the aqueous mixture is extracted with dichloroethane. The dichloroethane solution is evaporated, and the residue is subjected to fractional distillation in vacuo. 76.0 g (74.0%) of (±)-2-(propargyloxyimino)-1,7,7-trimethyl-bicyclo[2,2,1]heptane are obtained as a light yellow oil; b.p.: 92° C./1.0 mm Hg, nD20 =1.4956.
Reaction SMILES: B(Br)(Br)Br.ClCCl.C[O:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[NH:17][C:18]3[C:24]([C:25]([NH2:27])=[O:26])=[CH:23][CH:22]=[CH:21][C:19]=3[N:20]=2)=[CH:12][CH:11]=1>CO>[OH:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[NH:20][C:19]3[CH:21]=[CH:22][CH:23]=[C:24]([C:25]([NH2:27])=[O:26])[C:18]=3[N:17]=2)=[CH:14][CH:15]=1
Reactant: COc1ccc(-c2nc3cccc(C(N)=O)c3[nH]2)cc1
Agent: BrB(Br)Br
Solvent: CO
Solvent: ClCCl
Product: NC(=O)c1cccc2[nH]c(-c3ccc(O)cc3)nc12

Procedure:
Under an argon atmosphere 1M boron tribromide in dichloromethane (3.8 ml, 3.79 mmol) was transferred to a flask containing 2-(4'-methoxyphenyl)benzimidazole-4-carboxamide (NU 1076 from Example 5) (202.4 mg, 0.758 mmol). The resulting solution was refluxed for 24 hours using an air condenser. The solvent was removed by distillation to complete dryness. The solid residue was treated with 10% NaOH (10 ml), followed by dropwise addition of concentrated hydrochloric acid to neutralise (pH 7). The white precipitate was collected by filtration and dissolved in ethyl acetate (10 ml). The organic solvent was washed with water (2×3 ml), dried over MgSO4, and the product was obtained by removal of the solvent under reduced pressure. (109.5 mg, 57%). mp 266-267° C.; Found C, 63.27, H 4.37; N 15.67; C14H11N3O2. 0.75 MeOH requires C, 63.04; H, 4.69; N, 15.76; vmax (cm-1) 3424.01, 3384.16, 3309.20, 3249.55, 3155.62, 1642.35, 1618.02, 1594.50, 1577.74; δH 7.03-7.07 (2H, d, J=8.5), 7.34-7.42 (1H, t), 7.75-7.79 (1H, d), 7.85 (1H, br s), 7.90-7.94 (1H, d), 8.15-8.19 (2H, d, J=8.5), 9.4-9.6 (1H, br s), 10.0-10.4 (1H, br s), 13.0-13.4 (1H, br s); m/z (EI) 253 (M+), 236, 208, 93.
Reaction SMILES: [N:1]12[CH2:8][C:5]([C:9](=[O:30])[CH:10]=P(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)([CH2:6][CH2:7]1)[CH2:4][CH2:3][CH2:2]2.C1(C)C=CC=CC=1.[C:38]([O:42][CH2:43][CH3:44])(=[O:41])[CH:39]=O>C(Cl)(Cl)Cl>[N:1]12[CH2:8][C:5]([C:9](=[O:30])/[CH:10]=[CH:39]/[C:38]([O:42][CH2:43][CH3:44])=[O:41])([CH2:6][CH2:7]1)[CH2:4][CH2:3][CH2:2]2
Reactant: O=C(C=P(c1ccccc1)(c1ccccc1)c1ccccc1)C12CCCN(CC1)C2
Reactant: CCOC(=O)C=O
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Product: CCOC(=O)/C=C/C(=O)C12CCCN(CC1)C2
Temperature: 25 °C

Procedure:
5.00 g (12.09 mmol) of 1-(1-azabicyclo[3.2.1]oct-5-yl)-2-(triphenylphosphanylidene)-ethanone in solution in 20 ml of chloroform and 20 ml of toluene are introduced into a 100 ml three-necked round-bottomed flask. 1.36 g (13.3 mmol) of ethyl glyoxylate are subsequently added and the reaction medium is refluxed at ambient temperature for 15 min. The solvent is eliminated by evaporation under reduced pressure and the residue obtained is purified by silica gel column chromatography, elution being carried out with a mixture of chloroform, methanol and aqueous ammonia in the proportions 89/2/0.2.
Reaction SMILES: [OH:1][CH2:2][C:3]1[N:4]([CH2:20][CH3:21])[C:5]([S:11][C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[C:14]([Cl:19])[CH:13]=2)=[C:6]([CH:8]([CH3:10])[CH3:9])[N:7]=1.C(=O)([O-])N.[C:26]([N:43]=[C:44]=[O:45])(=[O:42])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]>>[C:26]([NH:43][C:44](=[O:45])[O:1][CH2:2][C:3]1[N:4]([CH2:20][CH3:21])[C:5]([S:11][C:12]2[CH:17]=[C:16]([Cl:18])[CH:15]=[C:14]([Cl:19])[CH:13]=2)=[C:6]([CH:8]([CH3:9])[CH3:10])[N:7]=1)(=[O:42])[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41]
Reactant: CCn1c(CO)nc(C(C)C)c1Sc1cc(Cl)cc(Cl)c1
Reactant: CCCCCCCCCCCCCCCC(=O)N=C=O
Agent: NC(=O)[O-]
Product: CCCCCCCCCCCCCCCC(=O)NC(=O)OCc1nc(C(C)C)c(Sc2cc(Cl)cc(Cl)c2)n1CC
Yield: 57 %

Procedure:
The compound 19 (250 mg, 0.725 mmol) was converted to the carbamate with palmitoyl isocyanate (5 eq.) in the same manner as the example 66 to give the compound 85 (259 mg, 57%). Mp. 95-97° C. Rf 0.33 (1:2 EtOAc - hexane).