Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:18]([CH2:19][C:20]([OH:22])=O)[C:13]3=[N:14][CH:15]=[CH:16][CH:17]=[C:12]3[N:11]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:23](N1C=CN=C1)([N:25]1C=CN=C1)=O.CN>O1CCCC1>[CH3:23][NH:25][C:20](=[O:22])[CH2:19][N:18]1[C:13]2=[N:14][CH:15]=[CH:16][CH:17]=[C:12]2[N:11]=[C:10]1[C:7]1[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:9][CH:8]=1
Reactant: O=C(O)Cn1c(-c2ccc([N+](=O)[O-])cc2)nc2cccnc21
Reactant: O=C(n1ccnc1)n1ccnc1
Agent: CN
Solvent: C1CCOC1
Product: CNC(=O)Cn1c(-c2ccc([N+](=O)[O-])cc2)nc2cccnc21
Temperature: 25 °C
Reaction time: 3 h
Yield: 13.4 %

Procedure:
A suspension of crude 2-(4-nitrophenyl)-3H-imidazo[4,5-b]pyridine-3-acetic acid (3.0 g, 0.0101 mole), 1,1'-carbonyldiimidazole (1.63 g, 0.0101 mole) and dry tetrahydrofuran (100 ml) was stirred at room temperature for three hours with a stream of nitrogen bubbling through it and then refluxed overnight under nitrogen. It was cooled to room temperature and a solution of methylamine (0.94 g, 0.0302 mole) in tetrahydrofuran (10 ml) was added and the reaction mixture was stirred at room temperature over the weekend. The solvents were removed under reduced pressure and the resulting solid was triturated in water, collected by filtration, rinsed once with water, once with 5% potassium hydroxide solution and once with water. The solid was dissolved in hot isopropyl alcohol, filtered hot and cooled in the refrigerator to precipitate a solid. Water was added and the solid was collected by filtration and dried under high vacuum at 70° C. to give 0.42 g (13%) of title compound, mp. >260° C.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:10][C:11]1[CH:12]=[C:13]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[N:14]([S:16]([C:19]2[CH:28]=[CH:27][CH:26]=[CH:25][C:20]=2[C:21]([O:23]C)=[O:22])(=[O:18])=[O:17])[CH:15]=1)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl>O1CCCC1.CO>[C:1]([O:5][C:6]([N:8]([CH2:10][C:11]1[CH:12]=[C:13]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[N:14]([S:16]([C:19]2[CH:28]=[CH:27][CH:26]=[CH:25][C:20]=2[C:21]([OH:23])=[O:22])(=[O:17])=[O:18])[CH:15]=1)[CH3:9])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COC(=O)c1ccccc1S(=O)(=O)n1cc(CN(C)C(=O)OC(C)(C)C)cc1-c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CN(Cc1cc(-c2ccccc2)n(S(=O)(=O)c2ccccc2C(=O)O)c1)C(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 1 h

Procedure:
Methyl 2-[(4-{[(tert-butoxycarbonyl) (methyl)amino]methyl}-2-phenyl-1H-pyrrol-1-yl)sulfonyl]benzoate (524 mg) was dissolved in tetrahydrofuran (5 mL) and methanol (3 mL), and 1 mol/L aqueous sodium hydroxide solution (3 mL) was added at 0° C. The mixture was stirred at 0° C. for 1 hr, and at room temperature for 16 hr, cooled again to 0° C., acidified with 1 mol/L hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=1:1→0:1) to give the title compound as a colorless amorphous (yield 256 mg, 50%).
Reaction SMILES: [C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[CH:13]=[C:12]([CH2:14][O:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)[C:11]([C:22]([F:25])([F:24])[F:23])=[CH:10][C:9]=1[NH2:26])([CH3:4])([CH3:3])[CH3:2].C([O:32][C:33](=O)[CH2:34][C:35]([C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([C:43]2[CH:48]=[CH:47][N:46]=[C:45]([CH3:49])[CH:44]=2)[CH:38]=1)=[O:36])(C)(C)C>>[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[CH:13]=[C:12]([CH2:14][O:15][CH:16]2[CH2:21][CH2:20][CH2:19][CH2:18][O:17]2)[C:11]([C:22]([F:24])([F:25])[F:23])=[CH:10][C:9]=1[NH:26][C:33](=[O:32])[CH2:34][C:35]([C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([C:43]2[CH:48]=[CH:47][N:46]=[C:45]([CH3:49])[CH:44]=2)[CH:38]=1)=[O:36])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1cc(COC2CCCCO2)c(C(F)(F)F)cc1N
Reactant: Cc1cc(-c2cccc(C(=O)CC(=O)OC(C)(C)C)c2)ccn1
Product: Cc1cc(-c2cccc(C(=O)CC(=O)Nc3cc(C(F)(F)F)c(COC4CCCCO4)cc3NC(=O)OC(C)(C)C)c2)ccn1

Procedure:
The title compound was prepared from [2-amino-5-(tetrahydro-pyran-2-yloxymethyl)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J38) (293 mg, 0.75 mmol) and 3-[3-(2-methyl-pyridin-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K12) (234 mg, 0.75 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (168 mg, 36%).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:11]2[O:12][C:13]3[C:19]([F:20])=[C:18]([F:21])[CH:17]=[CH:16][C:14]=3[N:15]=2)[C:7](F)=[CH:8][CH:9]=1)([O-:3])=[O:2].[CH2:22]([NH2:25])[CH2:23][CH3:24]>>[N+:1]([C:4]1[CH:5]=[C:6]([C:11]2[O:12][C:13]3[C:19]([F:20])=[C:18]([F:21])[CH:17]=[CH:16][C:14]=3[N:15]=2)[C:7]([NH:25][CH2:22][CH2:23][CH3:24])=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(F)c(-c2nc3ccc(F)c(F)c3o2)c1
Reactant: CCCN
Product: CCCNc1ccc([N+](=O)[O-])cc1-c1nc2ccc(F)c(F)c2o1

Procedure:
Prepared by the method of Example 54a), from 2-(3-nitro-6-fluorophenyl)-6,7-difluorobenzoxazole (235 mg, 0.8 mmol) and propylamine (328 μL, 4.0 mmol) the subtitle compound was obtained. The product was used directly in the next step without purification.
Reaction SMILES: [Cl:1][C:2]1[C:7](=[O:8])[N:6]([CH3:9])[CH:5]=[C:4]([NH:10][CH:11]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)[C:12]2[C:13]([C:24]([O:26]CC)=[O:25])=[N:14][N:15]([CH:21]3[CH2:23][CH2:22]3)[C:16]=2[C:17]([F:20])([F:19])[F:18])[CH:3]=1.[OH-].[Na+]>C1COCC1.CO>[Cl:1][C:2]1[C:7](=[O:8])[N:6]([CH3:9])[CH:5]=[C:4]([NH:10][CH:11]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)[C:12]2[C:13]([C:24]([OH:26])=[O:25])=[N:14][N:15]([CH:21]3[CH2:23][CH2:22]3)[C:16]=2[C:17]([F:19])([F:18])[F:20])[CH:3]=1
Reactant: CCOC(=O)c1nn(C2CC2)c(C(F)(F)F)c1C(Nc1cc(Cl)c(=O)n(C)c1)c1ccc(Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: Cn1cc(NC(c2ccc(Cl)cc2)c2c(C(=O)O)nn(C3CC3)c2C(F)(F)F)cc(Cl)c1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 77.9 %

Procedure:
To a solution of ethyl 4-(((5-chloro-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)amino)(4-chlorophenyl)methyl)-1-cyclopropyl-5-(trifluoromethyl)-1H-pyrazole-3-carboxylate (Step 40.3) (350 mg, 0.569 mmol) in THF (3 mL) and MeOH (3 mL) was added 2M NaOH (2.84 mL, 5.69 mmol). The resulting mixture was stirred at RT for 1 hr. Volatiles were evaporated and the resulting aq. phase was adjusted to pH 5 with 2N HCl, extracted twice with EtOAc and the combined organic phases were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude was triturated in EtOAc to afford the title product (222 mg, 0.443 mmol, 78% yield) as an off-white solid. tR: 1.00 min (LC-MS 2); ESI-MS: 501/503 [M+H]+, ESI-MS: 499/501 [M−H]− (LC-MS 2).
Reaction SMILES: C(=O)(O)[O-].[Na+].[Br:6][CH2:7][C:8](Br)=[O:9].[Cl:11][C:12]1[CH:13]=[C:14]([CH:22]=[CH:23][CH:24]=1)[O:15][CH:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.O>C(Cl)Cl>[Br:6][CH2:7][C:8]([N:19]1[CH2:18][CH2:17][CH:16]([O:15][C:14]2[CH:22]=[CH:23][CH:24]=[C:12]([Cl:11])[CH:13]=2)[CH2:21][CH2:20]1)=[O:9]
Reactant: O=C(Br)CBr
Reactant: Clc1cccc(OC2CCNCC2)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: O=C(CBr)N1CCC(Oc2cccc(Cl)c2)CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a suspension of sodium bicarbonate (34 g, 0.040 mol), 400 ml of methylene chloride and bromoacetyl bromide (15.7 ml, 36.5 g, 0.176 mol) cooled by an ice/salt bath was added dropwise a solution of 4-m-chlorophenoxypiperidine (34.9 g, 0.165 mol) in 400 ml of methylene chloride. The reaction mixture was stirred 1 hour at 0° and 3 hours at room temperature. The reaction mixture was poured into water, extracted with methylene chloride, and the extract was washed with water, 3N HCl, saturated sodium bicarbonate and saturated sodium chloride. Evaporation of the solvent provided N-(2-bromoacetyl)-4-(m-chlorophenoxy)piperidine.
Reaction SMILES: [CH:1]([NH2:4])([CH3:3])[CH3:2].[C:5]([CH2:8][C:9](=O)[CH3:10])(=[O:7])[CH3:6]>>[CH:1]([N:4]=[C:9]([CH2:8][C:5](=[O:7])[CH3:6])[CH3:10])([CH3:3])[CH3:2]
Reactant: CC(C)N
Reactant: CC(=O)CC(C)=O
Product: CC(=O)CC(C)=NC(C)C
Reaction time: 24 h

Procedure:
0.1 Mole (5.9 g.) isopropylamine is mixed with 0.1 mole (10 g.) acetylacetone. An exothermal reaction takes place in which a yellowish, crystalline ketimine is obtained which, after one day, slowly melts and then remains liquid.
Reaction SMILES: [NH2:1][C:2]1[C:3]([Cl:28])=[N:4][C:5]2[C:10]([C:11]=1[NH:12][CH2:13][CH2:14][CH:15]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]1)=[CH:9][CH:8]=[CH:7][CH:6]=2.Cl[C:30](Cl)([O:32]C(=O)OC(Cl)(Cl)Cl)Cl.C(=O)([O-])O.[Na+]>ClCCCl.C(N(CC)CC)C>[Cl:28][C:3]1[C:2]2[N:1]=[C:30]([OH:32])[N:12]([CH2:13][CH2:14][CH:15]3[CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:27])[CH3:26])=[O:22])[CH2:19][CH2:20]3)[C:11]=2[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:4]=1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: CC(C)(C)OC(=O)N1CCC(CCNc2c(N)c(Cl)nc3ccccc23)CC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCC(CCn2c(O)nc3c(Cl)nc4ccccc4c32)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 89.3 %

Procedure:
To a solution of 0.60 g of tert-butyl 4-[2-(3-amino-2-chloro-4-quinolylamino)-ethyl]-1-piperidinecarboxylate and 0.44 g of triphosgene in 10 ml of 1,2-dichloroethane, 0.41 ml of triethylamine was added dropwise, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was neutralized with saturated aqueous sodium hydrogencarbonate solution, and extracted with 1,2-dichloroethane. The extract was washed with saturated brine, and dried, and the solvent was evaporated. The residue was washed with diisopropyl ether to give 0.57 g of colorless crystals. Recrystallization from 1,2-dichloroethane gave colorless crystals having the melting point of from 222 to 223° C.
Reaction SMILES: [CH2:1]([OH:10])[C@@H:2]([C@H:4]([C@@H:6]([CH2:8][OH:9])[OH:7])[OH:5])[OH:3].[CH:11](=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.CO.OS(O)(=O)=O>O>[CH:11](=[C:1]([OH:10])[C@@H:2]([C@H:4]([C@@H:6]([CH2:8][OH:9])[OH:7])[OH:5])[OH:3])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: OC[C@@H](O)[C@H](O)[C@@H](O)CO
Reactant: O=Cc1ccccc1
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CO
Product: OC[C@@H](O)[C@H](O)[C@@H](O)C(O)=Cc1ccccc1

Procedure:
90 Parts by weight of xylitol (75 wt% aqueous solution), 42 parts by weight of benzaldehyde, 60 parts by weight of methanol, 6 parts by weight of conc. H2SO4 and 6 parts by weight of water were reacted with refluxing for two hours. After cooling, the solidified product was ground and washed with water and, then, neutralized with 10 wt% sodium hydroxide aqueous solution followed by washing with water and drying to obtain benzylidenexylitol.
Reaction SMILES: [N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][CH:2]=1.C(=O)([O-])[O-].[Cs+].[Cs+].I[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1>[Cu]I.CCCCCC.CN(C)C=O>[C:17]1([N:1]2[C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=[CH:2]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: Ic1ccccc1
Reactant: c1ccc2[nH]cnc2c1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCCCCC
Product: c1ccc(-n2cnc3ccccc32)cc1
Temperature: 110 °C
Yield: 45 %

Procedure:
In the dark, an oven-dried 50 ml round-bottomed flask containing a stir bar was charged with CuI (0.171 g, 0.1 eq.), benzimidazole (1.273 g, 1.2 eq.), and cesium carbonate (6.138 g, 2.1 eq.) respectively. The round-bottomed flask with the contents was sealed with septa and degassed with argon for 15 minutes. Iodobenzene (1 ml, 1 eq.), 1,10-Phenanthroline (0.323 g, 0.2 eq.), and dimethylformamide (25 ml) were then successively added into the round-bottomed flask under a continuous flow of argon. The reaction mixture was degassed with argon for 30 minutes. The reaction was stirred with heating via an oil bath at 110° C. for 24 hours in the dark under nitrogen. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. 10 ml of ethyl acetate was added into the concentrated reaction mixture. It was then filtered and washed with 30 ml of ethyl acetate. The filtrate was concentrated under vacuo to give the crude product. The crude product was purified by column chromatography on silica gel (40% ethyl acetate: 60% hexane as the eluent) providing 0.780 g of 1-Phenyl benzoimidazole (45% yield) as yellow liquid.
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[C:14]([F:20])=[CH:13][C:3]=1[CH2:4]P(=O)(OCC)OCC.O=[C:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1.[H-].[Na+]>O1CCCC1>[Cl:1][C:2]1[CH:16]=[C:15]([N+:17]([O-:19])=[O:18])[C:14]([F:20])=[CH:13][C:3]=1[CH:4]=[C:22]1[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: CCOP(=O)(Cc1cc(F)c([N+](=O)[O-])cc1Cl)OCC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(=Cc2cc(F)c([N+](=O)[O-])cc2Cl)CC1
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 28.5 %

Procedure:
Diethyl 2-chloro-5-fluoro-4-nitrobenzylphosphonate (4.06 g, 12.47 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (2.48 g, 12.47 mmol) were stirred in tetrahydrofuran (47.9 ml) and cooled in an ice bath. Sodium hydride (0.65 g, 16.21 mmol) was added and the reaction taken off the ice bath and stirred for 3.5 hours at room temperature. The reaction was quenched with water and extracted with dichloromethane, dried (magnesium sulphate), filtered and evaporated under reduced pressure. The crude material was purified by silica chromatography using a dichloromethane solvent system. The oil obtained was triturated with heptane and filtered to give the title compound as a yellow solid (1.32 g). 1H NMR (CDCl3, 400 MHz): δ 8.12 (d, 1H), 7.13 (d, 1H), 6.33 (s, 1H), 3.55 (t, 2H), 3.44 (t, 2H), 2.41 (t, 2H), 2.34 (t, 2H), 1.48 (s, 9H)
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([O:13]CC)=O)=[N:9][N:10]=2)[CH:7]=1.Cl.Cl.[F:18][C:19]1[CH:24]=[CH:23][C:22]([CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[C:21]([C:31]([F:34])([F:33])[F:32])[CH:20]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>C1COCC1.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([N:28]3[CH2:29][CH2:30][CH:25]([C:22]4[CH:23]=[CH:24][C:19]([F:18])=[CH:20][C:21]=4[C:31]([F:34])([F:32])[F:33])[CH2:26][CH2:27]3)=[O:13])=[N:9][N:10]=2)[CH:7]=1
Reactant: CCOC(=O)c1nnc2ccc(Br)cn12
Reactant: Fc1ccc(C2CCNCC2)c(C(F)(F)F)c1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(c1nnc2ccc(Br)cn12)N1CCC(c2ccc(F)cc2C(F)(F)F)CC1
Reaction time: 0.33 h

Procedure:
To a solution of ethyl 6-bromo-[1,2,4]triazolo[4,3-a]pyridine-3-carboxylate (81 mg, 0.30 mmol) in THF (2.5 mL) was added a solution of LiOH monohydrate (14 mg, 0.30 mmol) in H2O (1.7 mL). The mixture stirred for 20 min and was neutralized with 2 N HCl. The mixture was concentrated under reduced pressure. The obtained residue was diluted in DMF (3.2 mL) under an atmosphere of N2. To this mixture was added 4-(4-fluoro-2-(trifluoromethyl)phenyl)piperidine hydrochloride (85 mg, 0.30 mmol), benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (267 mg, 0.60 mmol), and diisopropylethylamine (0.15 mL, 0.91 mmol). The mixture was stirred at ambient temperature for 18 h. The resulting mixture was diluted with H2O (20 mL) and the resulting precipitate was collected by filtration. The obtained solids were chromatographed over silica gel (Isco CombiFlash Rf unit, 12 g Redisep column, 0 to 50% EtOAc in hexanes) to provide (6-bromo-[1,2,4]triazolo[4,3-a]pyridin-3-yl)(4-(4-fluoro-2-(trifluoromethyl)phenyl)piperidin-1-yl)methanone as an orange film (92 mg, 64%): 1H NMR (300 MHz, DMSO-d6) δ 9.13 (dd, J=1.7, 0.9 Hz 1H), 7.98 (dd, J=10, 0.9 Hz, 1H), 7.77-7.69 (m, 2H), 7.60-7.47 (m, 2H), 5.30-5.18 (m, 1H), 4.77-4.68 (m, 1H), 3.43-3.34 (m, 1H), 3.28-3.12 (m, 1H), 3.11-2.90 (m, 1H), 1.97-1.69 (m, 4H); ESI MS m/z 472 [M+H]+.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH:13]1[O:15][CH2:14]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:16]1[O:24][C:23]2[CH:22]=[CH:21][C:20]([OH:25])=[CH:19][C:18]=2[O:17]1>>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH:13]([OH:15])[CH2:14][O:25][C:20]1[CH:21]=[CH:22][C:23]2[O:24][CH2:16][O:17][C:18]=2[CH:19]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: Oc1ccc2c(c1)OCO2
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C1CO1
Product: CC(C)(C)OC(=O)N1CCC[C@H]1C(O)COc1ccc2c(c1)OCO2
Yield: 73.1 %

Procedure:
By the same procedure as in Example 26-B), while using (2S)1-(tert-butoxycarbonyl)-2-(1,2-epoxyethyl)Pyrrolidine (2.00 g) and (3,4-methylenedioxy)phenol (2.72 g), there was obtained 2.41 g of the title compound.
Reaction SMILES: [CH3:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][CH:6]=1)=[O:4].[BH4-].[Na+]>CO>[F:12][C:11]([F:13])([F:14])[C:8]1[CH:7]=[CH:6][C:5]([CH:3]([OH:4])[CH2:2][CH3:1])=[CH:10][CH:9]=1
Reactant: CCC(=O)c1ccc(C(F)(F)F)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CCC(O)c1ccc(C(F)(F)F)cc1
Reaction time: 3 h
Yield: 95 %

Procedure:
To 4-trifluoromethylpropiophenone (1.0 g, 5.0 mmol) in MeOH (25 mL, 0.20 M), was added NaBH4 (187 mg, 5,0 mmol). After 3 hours at RT, the reaction was concentrated in vacuo, partitioned between H2O and CH2Cl2, dried, filtered and concentrated to give the title compound as a white solid (0.97 g, 96%). 1H NMR (300 MHz, CHLOROFORM-D) δ ppm 0.93 (t, J=7.54 Hz, 3 H) 1.71-1.85 (m, 2 H) 1.85-1.92 (m, 1 H) 4.69 (td, J=6.41, 3.39 Hz, 1 H) 7.44-7.50 (m, 2 H) 7.61 (d, J=8.29 Hz, 2 H).
Reaction SMILES: [N:1]1([CH2:6][C:7]2[CH:12]=[CH:11][C:10]([N:13]3[CH2:18][CH2:17][CH:16]([CH:19]=O)[CH2:15][CH2:14]3)=[CH:9][CH:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:21][N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1>>[CH3:21][N:22]1[CH2:27][CH2:26][N:25]([CH2:19][CH:16]2[CH2:17][CH2:18][N:13]([C:10]3[CH:11]=[CH:12][C:7]([CH2:6][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)=[CH:8][CH:9]=3)[CH2:14][CH2:15]2)[CH2:24][CH2:23]1
Reactant: CN1CCNCC1
Reactant: O=CC1CCN(c2ccc(CN3CCCC3)cc2)CC1
Product: CN1CCN(CC2CCN(c3ccc(CN4CCCC4)cc3)CC2)CC1

Procedure:
Prepared from the product of Example 16 and N-methylpiperazine.
Reaction SMILES: [C:1]([O:4][CH:5]1[CH2:24][CH2:23][C@@:22]2([CH3:25])[C:7](=[CH:8][CH2:9][C@@H:10]3[C@@H:21]2[CH2:20][CH2:19][C@@:18]2([CH3:26])[C@H:11]3[CH2:12][CH:13]=[C:14]2[C:15](=[O:17])[CH3:16])[CH2:6]1)(=[O:3])[CH3:2].[CH3:27][Al](C)C.O>O1CCOCC1.C1(C)C=CC=CC=1.[Cu]Br>[C:1]([O:4][CH:5]1[CH2:24][CH2:23][C@@:22]2([CH3:25])[C:7](=[CH:8][CH2:9][C@@H:10]3[C@@H:21]2[CH2:20][CH2:19][C@@:18]2([CH3:26])[C@H:11]3[CH2:12][C@@H:13]([CH3:27])[C@@H:14]2[C:15](=[O:17])[CH3:16])[CH2:6]1)(=[O:3])[CH3:2]
Reactant: CC(=O)OC1CC[C@@]2(C)C(=CC[C@@H]3[C@@H]2CC[C@]2(C)C(C(C)=O)=CC[C@@H]32)C1
Reactant: C[Al](C)C
Agent: [Cu]Br
Solvent: O
Solvent: C1COCCO1
Solvent: Cc1ccccc1
Product: CC(=O)OC1CC[C@@]2(C)C(=CC[C@H]3[C@@H]4C[C@@H](C)[C@H](C(C)=O)[C@@]4(C)CC[C@@H]32)C1
Temperature: 20 °C
Reaction time: 0.17 h
Yield: 30 %

Procedure:
3.56 g (10 mmol) of 3-acetoxy-pregna-5,16-dien-20-one is dissolved in 20 ml of dioxane at 20° C. and mixed with 143.3 g (1 mmol) of copper(I) bromide. 9.4 ml (11 mmol) of a 10% solution of trimethyl aluminum in toluene is added to the reaction at room temperature under nitrogen atmosphere and, after completion of the addition, stirred for 10 minutes at 20° C. For hydrolysis of the reaction solution, 1 ml of water dissolved in 5 ml of dioxane is carefully added to the reaction. It is stirred for 10 minutes more and the inorganic precipitate filtered off with dioxane is washed again. The dioxane solution is concentrated by evaporation on a rotary evaporator and the residue is chromatographed on silica gel with ethyl acetate/hexane as eluent. After concentration by evaporation of the fractions, 1.12 g of 3-acetoxy-16α-methyl-pregn-5-en-20-one (30% of theory) is obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5](C)[N:4]([C:8](=[NH:19])[NH:9][S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)(=[O:12])=[O:11])N=1.CS(O)(=O)=O.N1CCCC1>>[NH2:19][C:8]([N:4]1[CH2:1][CH2:2][CH2:6][CH2:5]1)=[N:9][S:10]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)(=[O:11])=[O:12]
Reactant: Cc1cc(C)n(C(=N)NS(=O)(=O)c2ccccc2)n1
Agent: CS(=O)(=O)O
Solvent: C1CCNC1
Product: NC(=NS(=O)(=O)c1ccccc1)N1CCCC1

Procedure:
The compound of Example 26 was prepared according to the accompanying synthesis procedure from 0.5 ml of N-[(3,5-dimethylpyrazol-1-yl)-iminomethyl]-benzenesulfonamide solution (0.2 M, acetonitrile) with 19 mg of methanesulfonic acid and 0.5 ml of pyrrolidine solution (1.0 M, acetonitrile) and filed in a substance databank. Calculated mol. wt. 253.32; found mol. wt. (M+H) 254.3; 506.9 (Dimer)
Reaction SMILES: CC(C)(C)C(C1C(CC(C)(C)C(OCC)=O)=C(C(C2C=CC=CC=2)=O)N2C=1C=C(O)C=C2)=O.[Cl:34][C:35]1[CH:40]=[CH:39][C:38]([C:41]([C:43]2[N:51]3[C:46]([CH:47]=[C:48]([OH:52])[CH:49]=[CH:50]3)=[C:45]([C:53](=[O:58])[C:54]([CH3:57])([CH3:56])[CH3:55])[C:44]=2[CH2:59][C:60]([CH3:67])([CH3:66])[C:61]([O:63][CH2:64][CH3:65])=[O:62])=[O:42])=[CH:37][CH:36]=1.Cl.Cl[CH2:70][C:71]1[CH:80]=[CH:79][C:78]2[C:73](=[CH:74][CH:75]=[CH:76][CH:77]=2)[N:72]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:34][C:35]1[CH:36]=[CH:37][C:38]([C:41]([C:43]2[N:51]3[C:46]([CH:47]=[C:48]([O:52][CH2:70][C:71]4[CH:80]=[CH:79][C:78]5[C:73](=[CH:74][CH:75]=[CH:76][CH:77]=5)[N:72]=4)[CH:49]=[CH:50]3)=[C:45]([C:53](=[O:58])[C:54]([CH3:56])([CH3:57])[CH3:55])[C:44]=2[CH2:59][C:60]([CH3:66])([CH3:67])[C:61]([O:63][CH2:64][CH3:65])=[O:62])=[O:42])=[CH:39][CH:40]=1
Reactant: CCOC(=O)C(C)(C)Cc1c(C(=O)C(C)(C)C)c2cc(O)ccn2c1C(=O)c1ccc(Cl)cc1
Reactant: ClCc1ccc2ccccc2n1
Agent: CCOC(=O)C(C)(C)Cc1c(C(=O)C(C)(C)C)c2cc(O)ccn2c1C(=O)c1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)(C)Cc1c(C(=O)C(C)(C)C)c2cc(OCc3ccc4ccccc4n3)ccn2c1C(=O)c1ccc(Cl)cc1
Temperature: 23 °C
Reaction time: 24 h

Procedure:
To a stirred solution of ethyl 3-[7-(benzyloxy)-3-[(4-chlorophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)indolizin-2-yl]-2,2-dimethylpropanoate (3.50 g, 6.10 mmol) in EtOH (50 mL) is added 10% Pd/C (480 mg). The suspension is stirred under an atmosphere of hydrogen for 1.5 h then filtered through a pad of diatomaceous earth and washed with EtOH. The filtrate is concentrated in vacuo to give ethyl 3-{3-[(4-chlorophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)-7-hydroxyindolizin-2-yl}-2,2-dimethylpropanoate (2.50 g, 85%). Also obtained is ethyl 3-[1-(2,2-dimethylpropanoyl)-7-hydroxy-3-(phenylcarbonyl)indolizin-2-yl]-2,2-dimethylpropanoate (0.28 g, 10%). A suspension of ethyl 3-{3-[(4-chlorophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)-7-hydroxyindolizin-2-yl}-2,2-dimethylpropanoate (100 mg, 0.207 mmol), 2-(chloromethyl)quinoline-HCl (66.0 mg, 0.310 mmol), and potassium carbonate (114 mg, 0.826 mmol) in DMF (3 mL) is stirred for 24 h at 23° C. The mixture is filtered and concentrated in vacuo to give ethyl 3-{3-[(4-chlorophenyl)carbonyl]-1-(2,2-dimethylpropanoyl)-7-(quinolin-2-ylmethoxy)indolizin-2-yl}-2,2-dimethylpropanoate that is dissolved in THF (2 mL), MeOH (3 mL), and 6M aqueous NaOH (2 mL) and heated at 70° C. for 1 h then cooled to 23° C. and acidified to pH=1 with concentrated aqueous HCl. The mixture is partitioned between CH2Cl2 and brine then organics are dried with MgSO4, filtered, and concentrated in vacuo. Purification of the crude by HPLC (25 to 75% CH3CN/0.1% TFA in water) gives the title compound (60 mg, 49%).
Reaction SMILES: [CH:1]1([CH2:4][N:5]([CH2:18][CH2:19][OH:20])[C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[C:8]([C:14]([F:17])([F:16])[F:15])[CH:7]=2)[CH2:3][CH2:2]1.[CH3:21][O:22][C:23]1[CH:28]=[CH:27][C:26](O)=[CH:25][CH:24]=1>>[CH:1]1([CH2:4][N:5]([CH2:18][CH2:19][O:20][C:26]2[CH:27]=[CH:28][C:23]([O:22][CH3:21])=[CH:24][CH:25]=2)[C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[C:8]([C:14]([F:16])([F:17])[F:15])[CH:7]=2)[CH2:2][CH2:3]1
Reactant: N#Cc1ccc(N(CCO)CC2CC2)cc1C(F)(F)F
Reactant: COc1ccc(O)cc1
Product: COc1ccc(OCCN(CC2CC2)c2ccc(C#N)c(C(F)(F)F)c2)cc1

Procedure:
Synthesized as described in Example 1C from 4-[(cyclopropylmethyl)(2-hydroxyethyl)amino]-2-(trifluoromethyl)benzonitrile and 4-methoxyphenol: MS (APCI) m/z 391 (M+1).