Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][CH:3]=1.[C:12]1(B(O)O)[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[O:1]([C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:10][CH:11]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: COC(=O)c1ccc(O)cc1
Reactant: OB(O)c1ccccc1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: c1ccncc1
Solvent: ClCCl
Product: COC(=O)c1ccc(Oc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of methyl 4-hydroxybenzoate (0.200 g; 1.31 mmol), benzeneboronic acid (0.321 g; 2.63 mmol), copper acetate (0.477 g; 2.63 mmol) and pyridine (0.213 mL; 2.63 mmol) in dichloromethane (8 mL) was stirred at room temperature overnight. The reaction mixture was filtered and concentrated in vacuo.
Reaction SMILES: C([Li])CCC.[CH3:6][C:7]1[CH:11]=[C:10]([CH3:12])[O:9][N:8]=1.[C:13]([C:17]1[C:26]([O:27][SiH:28]([CH3:30])[CH3:29])=[CH:25][CH:24]=[CH:23][C:18]=1[C:19](OC)=[O:20])([CH3:16])([CH3:15])[CH3:14].[Cl-].[NH4+]>CCCCCC.O1CCCC1>[CH3:6][C:7]1[CH:11]=[C:10]([CH2:12][C:19]([C:18]2[CH:23]=[CH:24][CH:25]=[C:26]([O:27][SiH:28]([CH3:30])[CH3:29])[C:17]=2[C:13]([CH3:16])([CH3:15])[CH3:14])=[O:20])[O:9][N:8]=1
Reactant: COC(=O)c1cccc(O[SiH](C)C)c1C(C)(C)C
Reactant: Cc1cc(C)on1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: Cc1cc(CC(=O)c2cccc(O[SiH](C)C)c2C(C)(C)C)on1
Temperature: -20 °C
Yield: 50.4 %

Procedure:
52 ml of 1N solution of n-butyllithium in hexane were added to a solution of 6 g of 3,5-dimethylisoxazol in 200 ml of tetrahydrofuran at -78° C. After stirring for 1 h 15 g of methyl 2-tert.butyldimethylsiloxybenzoate in 50 ml of tetrahydrofuran were added at the same temperature. The reaction mixture was slowly warmed up to -20° C. A saturated aqueous solution of ammonium chloride was added, the mixture was extracted several times with ethylacetate. The organic phase was separated, washed with water and dried over magnesium sulfate. Chromatography on silica gel with heptane/ethylacetate gave 9.4 g of the product.
Reaction SMILES: CC(C)([O-])C.[K+].[OH:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[CH:11]2.C(OC([N:27]1[CH2:32][CH2:31][C:30](=O)[CH2:29][CH2:28]1)=O)C1C=CC=CC=1>C(O)(C)(C)C.C(OCC)(=O)C>[OH:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][CH:12]=[C:11]2[C:30]1[CH2:31][CH2:32][NH:27][CH2:28][CH:29]=1
Reactant: Oc1ccc2[nH]ccc2c1
Reactant: O=C1CCN(C(=O)OCc2ccccc2)CC1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC(C)(C)O
Product: Oc1ccc2[nH]cc(C3=CCNCC3)c2c1
Reaction time: 16 h
Yield: 92 %

Procedure:
Potassium tert-butoxide (2.81 g, 25.02 mmol) was added to a solution of 5-hydroxyindole (1.11 g, 8.34 mmol) in tert-butyl alcohol. 1-Benzyloxycarbonyl-4-piperidone (3.89 g, 16.67 mmol) was added to the purple reaction mixture at RT. After 16 h, the reaction mixture was diluted with ethyl acetate (100 ml) and washed with saturated sodium bicarbonate, brine, dried over MgSO4 and concentrated in vacuo. The residue was chromatographed (SiO2, 25-45% ethyl acetate/hexanes) to give 4-(5-hydroxyindol-3-yl)-1,2,3,6-tetrahydropyridine as a white solid (92%).
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3](=O)[CH2:4][C:5]([O:7]CC)=O.[C:13]1([NH:19][NH2:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(O)C>O>[C:13]1([N:19]2[C:5](=[O:7])[CH:4]=[C:3]([C:2]([F:1])([F:11])[F:12])[NH:20]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CCOC(=O)CC(=O)C(F)(F)F
Reactant: NNc1ccccc1
Solvent: O
Solvent: CCO
Product: O=c1cc(C(F)(F)F)[nH]n1-c1ccccc1
Reaction time: 1 h

Procedure:
A mixture of 184 parts of ethyl trifluoroacetoacetate, 120 parts of phenylhydrazine, 200 parts by volume of ethanol and 20 parts by volume of 22° Be hydrochloric acid was heated under reflux, with stirring, for one hour, then 500 parts of water were added and the product was cooled in ice. The yellow precipitate obtained was filtered off, drained, washed, with a small portion of chilled toluene until decoloration took place. Thereafter it was dried in an oven (50° C.). 215 parts of 1-phenyl-3-trifluoromethyl-5-pyrazolone was obtained of which the melting point was 193° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:33]=[C:8]2[N:9]=[CH:10][C:11]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[CH:21][CH:20]=3)=[C:12]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[N:7]2[N:6]=1)=[O:4].[Br:34]N1C(=O)CCC1=O>ClCCl>[CH3:1][O:2][C:3]([C:5]1[C:33]([Br:34])=[C:8]2[N:9]=[CH:10][C:11]([C:19]3[CH:20]=[CH:21][C:22]([O:25][CH2:26][C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)=[CH:23][CH:24]=3)=[C:12]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[N:7]2[N:6]=1)=[O:4]
Reactant: O=C1CCC(=O)N1Br
Reactant: COC(=O)c1cc2ncc(-c3ccc(OCc4ccccc4)cc3)c(C3CCCCC3)n2n1
Solvent: ClCCl
Product: COC(=O)c1nn2c(C3CCCCC3)c(-c3ccc(OCc4ccccc4)cc3)cnc2c1Br
Temperature: 25 °C
Reaction time: 8 h
Yield: 11.9 %

Procedure:
To an ice cold solution of 50 mg (0.113 mmol) of 6-(4-benzyloxy-phenyl)-7-cyclohexyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid methyl ester in 2 mL of dichloromethane (DCM) was added a solution of 21 mg (0.118 mmol) of N-bromosuccinimide (NBS) in 1 mL of DCM and the resulting mixture was allowed to warm up to rt and stirred at rt overnight. The reaction mixture was concentrated to give a residue which was chromatographed on silica gel (5% ethyl acetate in dichloromethane) to afford 7 mg (11% yield) of 6-(4-benzyloxy-phenyl)-3-bromo-7-cyclohexyl-pyrazolo[1,5-a]pyrimidine-2-carboxylic acid methyl ester as a colorless oil as indicated by 1H NMR (90% purity); LC-MS—calcd for C27H26BrN3O3 [M++H]+: 520.12, found: 520.0.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7](/[CH:10]=[CH:11]/[CH2:12][OH:13])=[CH:6][CH:5]=1)([O-:3])=[O:2].C([O:18]O)(C)(C)C>C(Cl)Cl.C(OCC)(=O)C>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C@@H:10]2[O:18][C@H:11]2[CH2:12][OH:13])=[CH:8][CH:9]=1)([O-:3])=[O:2]
Reactant: CC(C)(C)OO
Reactant: O=[N+]([O-])c1ccc(/C=C/CO)cc1
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: O=[N+]([O-])c1ccc([C@@H]2O[C@H]2CO)cc1
Temperature: -5 °C
Reaction time: 0.17 h
Yield: 97 %

Procedure:
A flame-dried 50 ml three-necked flask was fitted with a thermometer and a dropping funnel, flushed with nitrogen, and charged with a mixture of powdered, activated 3 Å molecular sieves (0.45 g) and dry CH2Cl2 (15 ml). After cooling to −5° C., L-(+)-diethyl tartrate (92.8 mg, 0.45 mmol) and Ti(O-i-Pr)4 (88.5 ul, 0.30 mmol) were added sequentially. The mixture was cooled to −20° C. in a CCl4 dry ice bath, (E)-3-(4-nitrophenyl)-2-propenol 4 (1.074 g, 6 mmol) (dissolved in dry methylene chloride (15 ml) and dried with 3Å molecular sieves for 10-15 min prior to addition) was added and the mixture was stirred for 10 minutes. A 7.0 M solution of t-butylhydroperoxide (TBHP) in CH2Cl2 (1.72 ml, 12 mmol) was added, taking care to maintain the temperature around −20° C. After stirring, at −20° C. for 2 hrs, the cold (−20° C.) reaction mixture was quenched with a 10% aqueous solution of sodium hydroxide saturated with sodium chloride (0.48 ml). Ether in the amount of 10% of the total volume of the reaction mixture was added, the cold bath removed and the stirred mixture allowed to warm to 10° C. Stirring was maintained for an additional 10 minutes at 10° C., whereupon anhydrous MgSO4 (0.48 g,) and Celite® (0.06 g) were added. After a final 15 min. of stirring, the mixture was allowed to settle and the clear solution was filtered through a pad of Celite® and washed with ethyl ether. Concentration of the ether solution gave the crude product containing TBHP, which was dissolved in a minimum amount of ethyl acetate, filtered through a small pad of silica gel, and recrystallized from CH2Cl2-hexanes to yield compound 5, (2S, 3S)-3-(4-nitrophenyl) oxiranemethanol (1.13 g, 97%) as light yellow needles: mp 100-101° C. (literature value: 98-99° C.); Rf=0.62 (5% CH3OH—CH2Cl2); 1H NMR (300 MHz, CDCl3) δ: 8.22 (d, aromatic, 2H, J=8.7 Hz), 7.45 (d, aromatic, 2H, J=8.7 Hz), 4.10 (m, 2H) 3.89 (m, 1H), 3.20 (m, 1H), 1.74 (m, 1H); 13C NMR (CDCl3): d 147.88(C), 144.35(C), 126.41(CH), 123.82(CH), 62.94(CH), 60.62(CH2), 54.30(CH). Anal. Calcd for C9H9NO4: C, 55.38; H, 4.65; N, 7.18. Found: C, 55-65; H, 4.54; N, 7.17.
Reaction SMILES: CC(C)([O-])C.[K+].[Cl:7][C:8]1[CH:13]=[C:12]([OH:14])[CH:11]=[CH:10][C:9]=1[CH:15]([CH3:34])[C:16]([C:22]1[CH:33]=[CH:32][C:25]2[N:26]([CH3:31])[C:27](=[O:30])[N:28]([CH3:29])[C:24]=2[CH:23]=1)([OH:21])[C:17]([F:20])([F:19])[F:18].Cl[C:36]1[N:45]=[CH:44][C:43]([Cl:46])=[CH:42][C:37]=1[C:38]([O:40][CH3:41])=[O:39].C(O)=O>CN(C=O)C>[CH3:41][O:40][C:38](=[O:39])[C:37]1[CH:42]=[C:43]([Cl:46])[CH:44]=[N:45][C:36]=1[O:14][C:12]1[CH:11]=[CH:10][C:9]([CH:15]([CH3:34])[C:16]([C:22]2[CH:33]=[CH:32][C:25]3[N:26]([CH3:31])[C:27](=[O:30])[N:28]([CH3:29])[C:24]=3[CH:23]=2)([OH:21])[C:17]([F:18])([F:19])[F:20])=[C:8]([Cl:7])[CH:13]=1
Reactant: COC(=O)c1cc(Cl)cnc1Cl
Reactant: CC(c1ccc(O)cc1Cl)C(O)(c1ccc2c(c1)n(C)c(=O)n2C)C(F)(F)F
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: O=CO
Solvent: CN(C)C=O
Product: COC(=O)c1cc(Cl)cnc1Oc1ccc(C(C)C(O)(c2ccc3c(c2)n(C)c(=O)n3C)C(F)(F)F)c(Cl)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Potassium tert-butoxide (6 mg) was added to a solution of 5-[2-(2-chloro-4-hydroxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1,3-dimethyl-1,3-dihydro-benzoimidazol-2-one (Example 85, 20 mg) in DMF (3.6 ml). The solution was added to methyl 2,5-dichloronicotinate (CAS Reg. No. 67754-03-4, 20 mg). The resulting mixture was stirred overnight at room temperature. The mixture was acidified with HCOOH and purified by prep. HPLC (C18-column, solvent gradient 20-98% CH3CN in 0.1% HCOOH[aq]) to give the title compound (10 mg). MS (m/e)=584.3 [M+H+].
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10](OC)=[O:11])=[CH:5][CH:4]=1.CC(C[AlH]CC(C)C)C.CCOCC>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][CH:10]=[O:11])=[CH:5][CH:4]=1
Reactant: COC(=O)Cc1ccc(OC)cc1
Agent: CC(C)C[AlH]CC(C)C
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: COc1ccc(CC=O)cc1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 90.4 %

Procedure:
To a stirred solution of methyl 4-methoxyphenylacetate (45.0 g) in toluene (250 ml) cooled to -78° C., add a 1.5M solution of DIBALH in toluene (167 ml) over 5 h, maintaining the reaction temperature at -78° C. Stir for an additional 0.5 h, then pour into 1:1 ice/1M HCl (1500 ml) and Et2O (500 ml). Stir the slurry for 1 h, separate the layers and extract the aq. layer with Et2O (2×500 ml). Wash the combined organic layers with sat'd NaHCO3 (500 ml) and sat'd NaCl, dry (MgSO4), filter and evaporate to give an oil. Perform bulb-to-bulb distillation (100°-130° C., 1 mmHg) to obtain the title compound (33.9 g, 90%) as a colorless liquid. 1H Nmr (CDCl3) δ9.71 (1H, t, J=2.4 Hz), 7.12 (2H, m), 6.89 (2H, m), 3.79 (3H, s) 3.61 (2H, m).
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][C:11]([CH2:15][N:16]2[CH2:21][CH2:20][N:19]([S:22]([C:25]3[CH2:26][O:27][C:28]4[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:29]=4[CH:30]=3)(=[O:24])=[O:23])[CH2:18][C:17]2=[O:36])([OH:14])[CH2:10][CH2:9]1)=O)(C)(C)C.Cl>C(OCC)(=O)C.CO>[Cl:35][C:33]1[CH:32]=[CH:31][C:29]2[CH:30]=[C:25]([S:22]([N:19]3[CH2:20][CH2:21][N:16]([CH2:15][C:11]4([OH:14])[CH2:12][CH2:13][N:8]([C:11]5[CH:12]=[CH:13][N:8]=[CH:9][CH:10]=5)[CH2:9][CH2:10]4)[C:17](=[O:36])[CH2:18]3)(=[O:23])=[O:24])[CH2:26][O:27][C:28]=2[CH:34]=1
Reactant: CC(C)(C)OC(=O)N1CCC(O)(CN2CCN(S(=O)(=O)C3=Cc4ccc(Cl)cc4OC3)CC2=O)CC1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CO
Product: O=C1CN(S(=O)(=O)C2=Cc3ccc(Cl)cc3OC2)CCN1CC1(O)CCN(c2ccncc2)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 87.7 %

Procedure:
To 1-[1-(tert-butoxycarbonyl)-4-hydroxypiperidin-4-ylmethyl]-4-(7-chloro-2H-benzopyran-3-sulfonyl)-2-piperazinone (150 mg) were added 4N hydrochloric acid in ethyl acetate (8 ml) and methanol (4 ml), and the mixture was stirred at room temperature for 30 minutes. The reaction solution was concentrated, and to the residue were added 4-chloropyridine hydrochloride (81 mg), triethylamine (81 mg) and ethanol (20 ml). The mixture was allowed to react in a sealed tube at 150° C. for 15 hours. The reaction solution was concentrated, and the residue was purified with silica gel column chromatography (dichloromethane:methanol containing 10% ammonia solution=10:1) to give colorless solid of the title compound (63 mg).
Reaction SMILES: [CH2:1]([O:15][C:16]1[CH:17]=[C:18]([N+:37]([O-])=O)[CH:19]=[CH:20][C:21]=1[O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[H][H]>[Pd].C1COCC1.C(OCC)(=O)C>[CH2:1]([O:15][C:16]1[CH:17]=[C:18]([NH2:37])[CH:19]=[CH:20][C:21]=1[O:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: [H][H]
Reactant: CCCCCCCCCCCCCCOc1ccc([N+](=O)[O-])cc1OCCCCCCCCCCCCCC
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCCCCCCCCCCCCOc1ccc(N)cc1OCCCCCCCCCCCCCC
Yield: 87.7 %

Procedure:
A mixture of 3.5 g of 3,4-bis(tetradecyloxy)nitrobenzene and 0.5 g of 10% palladium on carbon in 80 ml of THF and 40 ml of ethyl acetate was stirredin a hydrogen atmosphere for 4 hours when uptake ceased. The catalyst was removed by filtration and the filtrate was concentrated at reduced pressure to a solid which was recrystallized from ethyl acetate-hexane to give 2.9 g (88% yield, mp 55°-58°) of 3,4-bis (tetradecyloxy)benzenamine.
Reaction SMILES: [C:1]([O:5][CH3:6])(=[O:4])[C:2]#[CH:3].[Br-].[Br-].[Br-].[Al+3].[C:11]([O:14][C@@H:15]1[C@@:33]2([CH3:34])[C:19](=[CH:20][CH2:21][C@@H:22]3[C@@H:32]2[CH2:31][CH2:30][C@@:29]2([CH3:35])[C@H:23]3[CH2:24][CH2:25]/[C:26]/2=[CH:27]/[CH3:28])[CH2:18][C@@H:17]([O:36][C:37](=[O:39])[CH3:38])[CH2:16]1)(=[O:13])[CH3:12]>C(Cl)Cl>[CH3:6][O:5][C:1](=[O:4])[CH:2]=[CH:3][C@H:27]([C:26]1[C@:29]2([CH3:35])[C@H:23]([C@H:22]3[C@H:32]([CH2:31][CH2:30]2)[C@:33]2([CH3:34])[C:19]([CH2:18][C@@H:17]([O:36][C:37](=[O:39])[CH3:38])[CH2:16][C@@H:15]2[O:14][C:11](=[O:13])[CH3:12])=[CH:20][CH2:21]3)[CH2:24][CH:25]=1)[CH3:28]
Reactant: C#CC(=O)OC
Reactant: C/C=C1/CC[C@H]2[C@@H]3CC=C4C[C@@H](OC(C)=O)C[C@H](OC(C)=O)[C@]4(C)[C@H]3CC[C@]12C
Agent: [Al+3]
Agent: [Br-]
Solvent: ClCCl
Product: COC(=O)C=C[C@@H](C)C1=CC[C@H]2[C@@H]3CC=C4C[C@@H](OC(C)=O)C[C@H](OC(C)=O)[C@]4(C)[C@H]3CC[C@]12C
Reaction time: 0.25 h

Procedure:
To a stirred solution of 0.13 ml (1.5 mmol) of methyl propiolate in 10 ml of dry methylene chloride (over 4 A molecular sieves) under a nitrogen atmosphere was added 0.954 g (3.5 mmol) of aluminum tribromide. Immediately thereafter was added 398 mg (1 mmol) of Z-pregna-5,17(20)-diene-1α,3β-diol diacetate dissolved in 10 ml dry methylene chloride. The orange-colored solution was stirred for 15 min. A 2-ml sample was quenched with 5 ml of 10% aqueous potassium sodium tartrate salts. Analysis of the organic phase showed 20% of 1α,3β-diacetyloxychola-5,16,22-trien-24-oic acid methyl ester had formed (GC analysis).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[N:12]1[CH2:17][CH2:16][CH:15]([CH2:18][N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:14][CH2:13]1)[CH:7]=O)([O-:3])=[O:2].[OH:24][CH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1>>[N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][C:11]=1[N:12]1[CH2:13][CH2:14][CH:15]([CH2:18][N:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:16][CH2:17]1)[CH2:7][N:28]1[CH2:29][CH2:30][CH:25]([OH:24])[CH2:26][CH2:27]1)([O-:3])=[O:2]
Reactant: O=Cc1ccc(N2CCC(CN3CCCC3)CC2)c([N+](=O)[O-])c1
Reactant: OC1CCNCC1
Product: O=[N+]([O-])c1cc(CN2CCC(O)CC2)ccc1N1CCC(CN2CCCC2)CC1

Procedure:
Prepared from the product of Example 64 and 4-hydroxypiperidine.
Reaction SMILES: [C:1]([C:4]1[CH:8]=[C:7]([C:9]([NH:11][C@@H:12]([CH3:28])[CH2:13][N:14]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[C:21]([Cl:27])[CH:20]=3)=[N:15]2)=[O:10])[NH:6][N:5]=1)(=[O:3])[CH3:2].CCO.[BH4-].[Na+].Cl>O>[Cl:27][C:21]1[CH:20]=[C:19]([C:16]2[CH:17]=[CH:18][N:14]([CH2:13][C@@H:12]([NH:11][C:9]([C:7]3[NH:6][N:5]=[C:4]([CH:1]([OH:3])[CH3:2])[CH:8]=3)=[O:10])[CH3:28])[N:15]=2)[CH:24]=[CH:23][C:22]=1[C:25]#[N:26]
Reactant: CC(=O)c1cc(C(=O)N[C@@H](C)Cn2ccc(-c3ccc(C#N)c(Cl)c3)n2)[nH]n1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CC(O)c1cc(C(=O)N[C@@H](C)Cn2ccc(-c3ccc(C#N)c(Cl)c3)n2)[nH]n1
Reaction time: 8 h

Procedure:
(S)-3-acetyl-N-(1-(3-(3-chloro-4-cyanophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-5-carboxamide (100 mg; 0.25 mmol) and 5 ml of EtOH were put to reaction flask and sodium borohydride (19 mg; 0.5 mmol) was added slowly as EtOH suspension. The reaction was stirred overnight to completion. 0.5 ml of water and 1 ml of 0.5M HCl were added dropwise. The solution was evaporated to dryness, 20 ml of DCM was added and washed with 10 ml of 1 M NaHCO3 and 10 ml of water followed with drying over Na2SO4. After filtration and evaporation 76 mg (76%) of pure title compound was obtained. 1H-NMR (400 MHz; d6-DMSO): δ 1.11 (d, 3H), 1.38 (d, 3H), 4.22-4.48 (m, 3H), 4.74-4.84 (m, 1H), 4.41 (d, 1H), 6.40 (s, 1H), 6.94 (d, 1H), 7.81 (d, 1H), 7.92-8.05 (m, 2H), 8.09 (d, 1H), 8.20 (d, 1H), 13.04 (s, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]([CH2:25][CH2:26][NH:27]C(=O)OC(C)(C)C)[C:9]([C:11]1[S:24][C:14]2[C:15]3[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=3[O:17][CH2:18][CH2:19][C:13]=2[CH:12]=1)=[O:10].C(Cl)Cl.C(O)(C(F)(F)F)=O>>[NH2:27][CH2:26][CH2:25][N:8]([C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[Cl:1])[C:9]([C:11]1[S:24][C:14]2[C:15]3[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=3[O:17][CH2:18][CH2:19][C:13]=2[CH:12]=1)=[O:10]
Reactant: CC(C)(C)OC(=O)NCCN(C(=O)c1cc2c(s1)-c1ccccc1OCC2)c1ccccc1Cl
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: NCCN(C(=O)c1cc2c(s1)-c1ccccc1OCC2)c1ccccc1Cl

Procedure:
To a solution of tert-butyl 2-(N-(2-chlorophenyl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-2-carboxamido)ethylcarbamate (0.022 g, 0.36 mmol)/in DCM (0.400 mL, 4.93 mmol) was added a solution of 95% TFA/5% water. The reaction was monitored by LC/MS for desired product. Reaction mix concentrated in vacuo, taken into EA and washed with H20, dried (Na2SO4), concentrated and crude purified by preparative RP-HLPC to give 131 (yield=98% of theoretical). MS: (ESI+) 400.1
Reaction SMILES: [NH:1]1[CH:9]2[CH:4]([CH2:5][CH2:6][CH2:7][CH2:8]2)[CH2:3][CH:2]1[C:10]([O:12][CH2:13][CH3:14])=[O:11].[CH2:15]([O:22][C:23]([NH:25][C@H:26]([C:28](O)=[O:29])[CH3:27])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(OCC)(=O)C>[CH2:15]([O:22][C:23]([NH:25][C@H:26]([C:28]([N:1]1[CH:9]2[CH:4]([CH2:5][CH2:6][CH2:7][CH2:8]2)[CH2:3][C@@H:2]1[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:29])[CH3:27])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: C[C@H](NC(=O)OCc1ccccc1)C(=O)O
Reactant: CCOC(=O)C1CC2CCCCC2N1
Solvent: CCOC(C)=O
Product: CCOC(=O)[C@H]1CC2CCCCC2N1C(=O)[C@H](C)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
To a solution of 10.0 g of ethyl octahydroindole-2-carboxylate (prepared in as shown in paragraph A of this example) in 400 ml of ethyl acetate add 17.0 g of N-benzyloxycarbonyl-(S)-alanine, N-hydroxysuccinimide ester. Stir the reaction mixture at room temperature for 20 hours and concentrate it in vacuo. Place the residue on a column of silica gel (3000 g, 60-200 mesh) and elute with chloroform:ethyl acetate 10:1 to give 1-[N-benzyloxycarbonyl-(S)-alanyl]octahydroindole-2(R)-carboxylic acid, ethyl ester, a colorless oil [α]D26 +22.0° (ethanol) and 1-[N-benzyloxycarbonyl-(S)alanyl]octahydroindole-2(S)-carboxylic acid, ethyl ester, a colorless oil [α]D26 -96.4° (ethanol).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([CH3:21])([CH3:20])[CH2:10][NH:11][CH2:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][CH:14]2[NH2:19])=[CH:4][CH:3]=1.C1([O:28][C:29](=O)[NH:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]3[N:41]([CH3:42])[N:40]=[N:39][N:38]=3)[CH:32]=2)C=CC=CC=1>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][C:9]([CH3:21])([CH3:20])[CH2:10][NH:11][CH2:12][C@@H:13]2[CH2:18][CH2:17][CH2:16][CH2:15][C@H:14]2[NH:19][C:29]([NH:30][C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([C:37]3[N:41]([CH3:42])[N:40]=[N:39][N:38]=3)[CH:32]=2)=[O:28])=[CH:6][CH:7]=1
Reactant: CC(C)(CNCC1CCCCC1N)Cc1ccc(F)cc1
Reactant: Cn1nnnc1-c1cccc(NC(=O)Oc2ccccc2)c1
Product: Cn1nnnc1-c1cccc(NC(=O)N[C@@H]2CCCC[C@H]2CNCC(C)(C)Cc2ccc(F)cc2)c1

Procedure:
Using the amine from Step e and [3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-carbamic acid phenyl ester, the titled compound was prepared by the methods desribed in Step d of Example 2.
Reaction SMILES: [OH-].[Na+].[O:3]1[CH:7]=[CH:6][CH:5]=[C:4]1[CH2:8][SH:9].Cl[C:11]1[CH:16]=[CH:15][N+:14]([O-:17])=[C:13]([CH3:18])[C:12]=1[CH3:19]>O1CCOCC1.O>[CH3:18][C:13]1[C:12]([CH3:19])=[C:11]([S:9][CH2:8][C:4]2[O:3][CH:7]=[CH:6][CH:5]=2)[CH:16]=[CH:15][N+:14]=1[O-:17]
Reactant: SCc1ccco1
Reactant: Cc1c(Cl)cc[n+]([O-])c1C
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: Cc1c(SCc2ccco2)cc[n+]([O-])c1C
Reaction time: 0.25 h

Procedure:
6 g of (60%) NaOH are added in portions to 50 ml of dry dioxane, the mixture is stirred for 15 minutes, 11.7 g (0.11 mol) of 2-furylmethylmercaptan are metered in, in the course of 20 minutes, and the mixture is again stirred for 30 minutes until the evolution of gas has ceased. A solution of 14.4 g (0.1 mol) of 4-chloro-2,3-dimethylpyridine N-oxide in 100 ml of dioxane is subsequently added dropwise in the course of 20 minutes, the reaction mixture is stirred at RT for 1 h, subsequently at 70° C. for 1 h and thereupon at 100° C. for a further 1 h. After the reaction has ended, the mixture is allowed to cool, diluted with 500 ml of water and extracted 4 times using in each case 300 ml of ethyl acetate. The combined organic phases are washed with water, dried over magnesium sulfate, concentrated and crystallized by adding diisopropyl ether. This gives 18.8 g (80% of theory) of 2,3-dimethyl-4-(2-furylmethylthio)pyridine N-oxide of m.p. 111°-112° C.
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[C:14]2[C:5]([NH:6][C:7]3[CH2:8][CH:9]([C:18]4[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=4)[CH2:10][C:11](=O)[C:12]=3[C:13]2=[O:16])=[CH:4][CH:3]=1.[CH3:28][N:29]([CH3:34])[CH2:30][CH2:31][CH2:32][NH2:33]>>[Cl:1][C:2]1[CH:15]=[C:14]2[C:5]([NH:6][C:7]3[CH2:8][CH:9]([C:18]4[CH:19]=[CH:20][C:21]([C:24]([F:26])([F:27])[F:25])=[CH:22][CH:23]=4)[CH2:10][C:11](=[N:33][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[CH3:28])[C:12]=3[C:13]2=[O:16])=[CH:4][CH:3]=1
Reactant: O=C1CC(c2ccc(C(F)(F)F)cc2)Cc2[nH]c3ccc(Cl)cc3c(=O)c21
Reactant: CN(C)CCCN
Product: CN(C)CCCN=C1CC(c2ccc(C(F)(F)F)cc2)Cc2[nH]c3ccc(Cl)cc3c(=O)c21

Procedure:
By following the above procedure and using 7-chloro3-[4-(trifluoromethyl)phenyl]-3,4-dihydro-1,9(2H,10H)acridinedione instead of 7-chloro-3-(3,4-dichlorophenyl)-3,4-dihydro-1,9(2H,10H)-acridinedione and N,N-dimethyl-1,3-propanediamine instead of N,N-diethylenediamine one obtains 7-chloro-1-[[3-(dimethylamino)propyl]imino]-1,3,4,10-tetrahydro-3-[4-(trifluoromethyl)phenyl]-9(2H)-acridinone; mp 211°-213° C. after recrystallization from ethanol.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][O:5][C:6]=1[C:7]1[CH:12]=[CH:11][C:10]([S:13](Cl)(=[O:15])=[O:14])=[CH:9][CH:8]=1.[NH2:17][C:18]1[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=1[C:25]([C:27]1[CH:28]=[N:29][C:30]([CH3:33])=[CH:31][CH:32]=1)=[O:26]>>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([NH:17][S:13]([C:10]2[CH:11]=[CH:12][C:7]([C:6]3[O:5][CH:4]=[N:3][C:2]=3[CH3:1])=[CH:8][CH:9]=2)(=[O:15])=[O:14])=[C:19]([C:25]([C:27]2[CH:28]=[N:29][C:30]([CH3:33])=[CH:31][CH:32]=2)=[O:26])[CH:20]=1
Reactant: Cc1ccc(C(=O)c2cc(Cl)ccc2N)cn1
Reactant: Cc1ncoc1-c1ccc(S(=O)(=O)Cl)cc1
Product: Cc1ccc(C(=O)c2cc(Cl)ccc2NS(=O)(=O)c2ccc(-c3ocnc3C)cc2)cn1

Procedure:
The title compound was prepared according to the general procedure for the preparation of N-aryl-benzenesulfonamides using by the reaction of 4-(4-methyl-oxazol-5-yl)-benzenesulfonyl chloride with (2-amino-5-chloro-phenyl)-(6-methyl-pyridin-3-yl)-methanone and purified by HPLC: MS: m/z 468.0 (M++1).