Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]([C:3]1[N:8]=[CH:7][C:6]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:16][OH:17])=[CH:5][CH:4]=1)[NH2:2].[C:18](Cl)(=[O:22])[CH:19]([CH3:21])[CH3:20]>>[CH:11]([C:16]1[N:8]2[CH:7]=[C:6]([O:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[CH2:16][O:17][C:18](=[O:22])[CH:19]([CH3:21])[CH3:20])[CH:5]=[CH:4][C:3]2=[N:1][N:2]=1)([CH3:12])[CH3:10]
Reactant: CC(C)C(=O)Cl
Reactant: NNc1ccc(Oc2ccccc2CO)cn1
Product: CC(C)C(=O)OCc1ccccc1Oc1ccc2nnc(C(C)C)n2c1
Temperature: 105 °C
Yield: 77 %

Procedure:
A mixture of {2-(6-hydrazino-pyridin-3-yloxy)-phenyl]-methanol (231 mg, 1 mmol) and isobutyryl chloride (938 μL, 9 mmol) was heated at 105° C. for 3 hours. The reaction was cooled to ambient temperature and quenched with saturated NaHCO3. The aqueous was extracted with ethyl acetate and the organics combined, dried over sodium sulfate, and concentrated in vacuo to an oil. The residue was purified by flash chromatography (eluting with 2% methanol/ethyl acetate) to give the title compound (136 mg, 39% for two steps).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH:20]=O)=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:29].[CH3:30][O:31][CH2:32][CH2:33][NH2:34].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:13]3[C:18]([CH:19]=2)=[CH:17][C:16]([CH2:20][NH:34][CH2:33][CH2:32][O:31][CH3:30])=[CH:15][CH:14]=3)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:29]
Reactant: CC(C)(C)OC(=O)n1c(-c2ccc(Cl)c3c2C(=O)NC3)cc2cc(C=O)ccc21
Reactant: COCCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Product: COCCNCc1ccc2c(c1)cc(-c1ccc(Cl)c3c1C(=O)NC3)n2C(=O)OC(C)(C)C

Procedure:
In a similar manner to Step. 1 of Example 56, 4-chloro-7-[1-(tert-butoxycarbonyl)-5-formylindol-2-yl]isoindolinone (20.0 mg, 0.0487 mmol) was dissolved in dichloromethane (0.5 mL). The solution was treated with 2-methoxyethylamine (0.017 mL, 0.20 mmol) and sodium triacetoxyborohydride (32 mg, 0.15 mmol) to obtain 4-chloro-7-[1-(tert-butoxycarbonyl)-5-[(2-methoxyethyl)aminomethyl]indol-2-yl]isoindolinone.
Reaction SMILES: [O:1]1[CH2:5][CH2:4][CH2:3][C@@H:2]1[CH2:6][O:7][C:8]1[CH:9]=[C:10]2[C:15](=[CH:16][CH:17]=1)[C:14](=[O:18])O[CH:12]=[CH:11]2.[Br:19][C:20]1[CH:25]=[CH:24][C:23]([NH2:26])=[CH:22][C:21]=1[F:27]>>[Br:19][C:20]1[CH:25]=[CH:24][C:23]([N:26]2[CH:12]=[CH:11][C:10]3[C:15](=[CH:16][CH:17]=[C:8]([O:7][CH2:6][C@H:2]4[CH2:3][CH2:4][CH2:5][O:1]4)[CH:9]=3)[C:14]2=[O:18])=[CH:22][C:21]=1[F:27]
Reactant: O=c1occc2cc(OC[C@H]3CCCO3)ccc12
Reactant: Nc1ccc(Br)c(F)c1
Product: O=c1c2ccc(OC[C@H]3CCCO3)cc2ccn1-c1ccc(Br)c(F)c1

Procedure:
6-[(R)-1-(Tetrahydrofuran-2-yl)methoxy]-isochromen-1-one and 4-bromo-3-fluorophenylamine were reacted according to Method AJ. In this way the product was obtained with molecular weight 418.27 (C20H17BrFNO3); MS (ESI): 418 and 420 (M+H+).
Reaction SMILES: [Br:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[Cl:19])[N:7]([CH2:20][CH2:21][CH2:22]Cl)[C:6]=2[C:5]([C:24]([O:26][CH3:27])=[O:25])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:24]([O:26][CH3:27])=[O:25])=[C:6]2[C:10]=1[N:9]=[C:8]1[N:11]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[Cl:19])[CH2:22][CH2:21][CH2:20][N:7]21
Reactant: COC(=O)c1ccc(Br)c2nc(Nc3ccc(Cl)cc3Cl)n(CCCCl)c12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(Br)c2nc3n(c12)CCCN3c1ccc(Cl)cc1Cl
Temperature: 80 °C
Reaction time: 0.25 h
Yield: 92 %

Procedure:
A mixture of above crude methyl 4-bromo-1-(3-chloropropyl)-2-[(2,4-dichlorophenyl)amino]-1H-benzimidazole-7-carboxylate and potassium carbonate (205 mg, 1.49 mmol) in N,N-dimethylformamide (10 mL) was stirred at 80° C. for 15 min. After ethyl acetate was added, the resultant mixture was washed with water and brine, dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 10-40% ethyl acetate/n-hexane gradient mixture to give the title compound as a colorless solid (414 mg, 0.910 mmol, 92%).
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[N:2]1.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C@@:13]1([CH2:17][N:18]2[CH:22]=[N:21][CH:20]=[N:19]2)[C@H:15]([CH3:16])[O:14]1>>[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C@:13]([OH:14])([C@H:15]([N:1]1[CH:5]=[CH:4][N:3]=[N:2]1)[CH3:16])[CH2:17][N:18]1[CH:22]=[N:21][CH:20]=[N:19]1
Reactant: c1c[nH]nn1
Reactant: C[C@@H]1O[C@@]1(Cn1cncn1)c1ccccc1F
Product: C[C@@H](n1ccnn1)[C@](O)(Cn1cncn1)c1ccccc1F

Procedure:
Using 1H-1,2,3-triazole and (2R,3S)-2-(2-fluorophenyl)-3-methyl-2-[(1H-1,2, 4-triazol-1-yl)methyl]oxirane, Compound 44 and Compound 45 were obtained by the same way as in Example 30.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[CH:13]=[C:12]4[CH2:15][CH2:16][CH2:17][C:18](=[O:19])[C:11]4=[CH:10][C:9]=3[O:8][CH2:7][C:6]=2[CH:20]=1.[CH:21]([B-](F)(F)F)=[CH2:22].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.C([O-])([O-])=O.[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].C(O)CC>[CH:21]([C:2]1[CH:3]=[CH:4][C:5]2[C:14]3[CH:13]=[C:12]4[CH2:15][CH2:16][CH2:17][C:18](=[O:19])[C:11]4=[CH:10][C:9]=3[O:8][CH2:7][C:6]=2[CH:20]=1)=[CH2:22]
Reactant: C=C[B-](F)(F)F
Reactant: O=C1CCCc2cc3c(cc21)OCc1cc(Cl)ccc1-3
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: COc1cccc(OC)c1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Solvent: CCCO
Product: C=Cc1ccc2c(c1)COc1cc3c(cc1-2)CCCC3=O
Temperature: 25 °C
Yield: 584.1 %

Procedure:
A 3-neck oven-dried 500 mL round-bottom flask was cooled under Ar, then charged with 3-Chloro-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (12.0 g, 42.1 mmol), potassium vinyltrifluoroborate (8.47 g, 6.32 mmol), Pd(OAc)2 (473 mg, 2.11 mmol), SPhos (1.74 g, 4.25 mmol), K2CO3 (17.5 g, 126 mmol) and anhydrous propanol (120 mL). The reaction mixture was sparged with Ar for 16 min, then heated to reflux for 5.5 h. Upon completion, the reaction mixture was cooled to RT and concentrated under reduced pressure. The crude residue was suspended in DCM, then washed with H2O and brine. The organic solution was dried over MgSO4, filtered and concentrated under reduced pressure. The resulting residue was further purified via silica plug, eluting with DCM to afford 3-vinyl-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (10.2 g, 87%).
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:6]([CH3:8])([CH3:7])[O:5][B:4]([C:9]2[CH:10]=[N:11][NH:12][CH:13]=2)[O:3]1.[C:15]([O:19][C:20]([N:22]1[CH2:26][CH2:25][C@H:24](OS(C)(=O)=O)[CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[C:15]([O:19][C:20]([N:22]1[CH2:26][CH2:25][C@@H:24]([N:12]2[CH:13]=[C:9]([B:4]3[O:5][C:6]([CH3:7])([CH3:8])[C:2]([CH3:14])([CH3:1])[O:3]3)[CH:10]=[N:11]2)[CH2:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]
Reactant: CC1(C)OB(c2cn[nH]c2)OC1(C)C
Reactant: CC(C)(C)OC(=O)N1CC[C@H](OS(C)(=O)=O)C1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CC[C@@H](n2cc(B3OC(C)(C)C(C)(C)O3)cn2)C1
Temperature: 25 °C

Procedure:
A solution of 4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.856 g, 4.41 mmol), (S)-3-methanesulfonyloxypyrrolidine-1-carboxylic acid tert-butyl ester (1.17 g, 4.41 mmol), and Cs2CO3 (2.16 g, 6.61 mmol) in anhydrous DMF (11.7 mL) was heated to 100° C. for 16 h. The re mixture was allowed to cool to rt and was partitioned between EtOAc and H2O and separated. The aqueous layer was re-extracted with EtOAc (3×) and the combined organic fractions were washed with H2O (3×), brine (2×), dried over Na2SO4, filtered and concentrated in vacuo resulting in a crude brown oil. The reaction mixture was purified by chromatography on silica gel [eluting with 12% EtOAc in CHCl3] resulting in the title compound as a light yellow oil. 1H NMR (400 MHz, CDCl3): δ=1.31 (s, 12H), 1.46 (s, 9H), 2.36 (q, J=7.0 Hz, 2H), 3.46-3.78 (m, 3H), 3.80-3.91 (m, 1H), 4.89 (quint, J=6.1 Hz, 1H), 7.73 (s, 1H), 7.80 (s, 1H).
Reaction SMILES: [CH:1]1([CH:7]([C:9]2[C:10]([CH:22]([CH3:24])[CH3:23])=[N:11][N:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[CH:13]=2)O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:25][C:26]1[CH:31]=[CH:30][C:29]([C:32]([NH:34][CH2:35][CH2:36][C:37]([O:39]CC)=[O:38])=[O:33])=[CH:28][CH:27]=1>>[CH:1]1([CH:7]([NH:25][C:26]2[CH:27]=[CH:28][C:29]([C:32]([NH:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:33])=[CH:30][CH:31]=2)[C:9]2[C:10]([CH:22]([CH3:24])[CH3:23])=[N:11][N:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: COc1ccc(-n2cc(C(O)C3CCCCC3)c(C(C)C)n2)cc1
Reactant: CCOC(=O)CCNC(=O)c1ccc(N)cc1
Product: COc1ccc(-n2cc(C(Nc3ccc(C(=O)NCCC(=O)O)cc3)C3CCCCC3)c(C(C)C)n2)cc1
Yield: 30.8 %

Procedure:
Using cyclohexyl[1-(4-methoxyphenyl)-3-(1-methylethyl)-1H-pyrazol-4-yl]methanol (0.70 g) synthesized above and ethyl 3-{[(4-aminophenyl)carbonyl]amino}propanoate (0.52 g) synthesized in Example 1(2) and in the same manner as in Example 1(7), the title object compound (0.34 g, 30%) was obtained as a white solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:17]2[C:22](=[O:23])[NH:21][C:20](=[O:24])[CH2:19][N:18]2[CH3:25])[CH:5]=[C:6]([Cl:16])[C:7]=1[S:8][C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=1.[H-].[Na+].[CH3:28]I>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([N:17]2[C:22](=[O:23])[N:21]([CH3:28])[C:20](=[O:24])[CH2:19][N:18]2[CH3:25])[CH:5]=[C:6]([Cl:16])[C:7]=1[S:8][C:9]1[CH:10]=[CH:11][C:12]([CH3:15])=[CH:13][CH:14]=1
Reactant: Cc1ccc(Sc2c(Cl)cc(N3C(=O)NC(=O)CN3C)cc2Cl)cc1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ccc(Sc2c(Cl)cc(N3C(=O)N(C)C(=O)CN3C)cc2Cl)cc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
0.7 g of 2-[3,5-dichloro-4-(4-methylthiophenoxy)phenyl]-1-methylhexahydro-1,2,4-triazine-3,5-dione (Example 2) was dissolved in 5 ml of cold dimethylformamide. About 200 mg of a suspension (about 50%)of sodium hydride were added and, when evolution of gases was complete, 1 ml of methyl iodide was added dropwise, and the mixture was stirred at room temperature for 4 hours. After acidification with 2N HCl, extraction with methylene chloride and evaporation were carried out, and the remaining oil was triturated with petroleum ether, whereupon it crystallized; melting point 148° C. after recrystallization from isopropanol.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]=[C:12]1[S:16][CH2:15][C:14]2([CH2:20][CH2:19][CH2:18][CH2:17]2)[NH:13]1.Br[CH2:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][O:24]1>>[CH3:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[N:11]=[C:12]1[S:16][CH2:15][C:14]2([CH2:17][CH2:18][CH2:19][CH2:20]2)[N:13]1[CH2:22][CH:23]1[CH2:28][CH2:27][CH2:26][CH2:25][O:24]1
Reactant: BrCC1CCCCO1
Reactant: Cc1cc([N+](=O)[O-])ccc1N=C1NC2(CCCC2)CS1
Product: Cc1cc([N+](=O)[O-])ccc1N=C1SCC2(CCCC2)N1CC1CCCCO1

Procedure:
1-Hydroxymethylcyclopentanamine was prepared according to Method B1c. The 2-hydroxyethylamine was converted to 1-chloromethylcyclopentanamine HCl salt according to Method B7e. 1-Chloromethylcyclopentanamine HCl salt was reacted with 2-methyl-4-nitrophenyl isothiocyanate according to Method C1e to give 2-(2-methyl-4-nitrophenylimino)-3-thia-1-azaspiro[4.4]nonane. The thiazolidine was reacted with 2-(bromomethyl)tetrahydro-2H-pyran according to Method D2e to give 2-(2-methyl-4-nitrophenylimino)-1-(tetrahydro-2H-pyran-2-ylmethyl)-3-thia-1-azaspiro[4.4]nonane.
Reaction SMILES: Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]([CH3:11])[CH:7]=[N:8]2)=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[S:19]([CH:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])[N:3]=1.[CH:25]([O:28][C:29]1[CH:35]=[C:34]([CH:36]2[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]2)[C:33]([CH3:43])=[CH:32][C:30]=1[NH2:31])([CH3:27])[CH3:26].CC1C=CC(S(O)(=O)=O)=CC=1>C(O)(C)C>[CH:25]([O:28][C:29]1[CH:35]=[C:34]([CH:36]2[CH2:37][CH2:38][N:39]([CH3:42])[CH2:40][CH2:41]2)[C:33]([CH3:43])=[CH:32][C:30]=1[NH:31][C:2]1[N:10]=[C:9]2[C:5]([N:6]([CH3:11])[CH:7]=[N:8]2)=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[S:19]([CH:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])[N:3]=1)([CH3:27])[CH3:26]
Reactant: CC(C)S(=O)(=O)c1ccccc1Nc1nc(Cl)nc2ncn(C)c12
Reactant: Cc1cc(N)c(OC(C)C)cc1C1CCN(C)CC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC(C)O
Product: Cc1cc(Nc2nc(Nc3ccccc3S(=O)(=O)C(C)C)c3c(ncn3C)n2)c(OC(C)C)cc1C1CCN(C)CC1
Temperature: 150 °C
Reaction time: 3 h

Procedure:
To a suspension of 2-chloro-N-(2-(isopropylsulfonyl)phenyl)-7-methyl-7H-purin-6-amine (1 equivalent) in isopropanol, was added 2-isopropoxy-5-methyl-4-(1-methylpiperidin-4-yl)aniline (1 equivalent) and 4-methylbenzenesulfonic acid (1 equivalent). The suspension was stirred at 150° C. for 3 hours, cooled to room temperature and the solvent evaporated. The residue was purified using a preparative HPLC to afford the desired product as a gummy solid.
Reaction SMILES: [Cl:1][C:2]1[N:6]([CH:7]([F:9])[F:8])[C:5]([CH3:10])=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1.[N+:18]([O-])([OH:20])=[O:19]>>[Cl:1][C:2]1[N:6]([CH:7]([F:8])[F:9])[C:5]([CH3:10])=[N:4][C:3]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([N+:18]([O-:20])=[O:19])[CH:12]=1
Reactant: O=[N+]([O-])O
Reactant: Cc1nc(-c2ccc(Cl)cc2)c(Cl)n1C(F)F
Product: Cc1nc(-c2ccc(Cl)c([N+](=O)[O-])c2)c(Cl)n1C(F)F
Temperature: 0 °C
Reaction time: 2 h

Procedure:
8 g (28 mmol) of 5-chloro-4-(4-chlorophenyl)-1-difluoromethyl-2-methyl-1H-imidazole were cooled to (−40)° C., and 100 ml of concentrated nitric acid were added. After 2 hours at (−20)° C., the mixture was poured into ice-water, whereupon the solid product of value was filtered off, washed with water and dried. Yield: 7 g.
Reaction SMILES: CC(C)([O-])C.[K+].[CH:7]([O:10][CH2:11][CH2:12][OH:13])([CH3:9])[CH3:8].[Cl:14][C:15]1[CH:23]=[CH:22][C:21](F)=[CH:20][C:16]=1[C:17]([OH:19])=[O:18].Cl>CN1C(=O)CCC1.O>[Cl:14][C:15]1[CH:23]=[CH:22][C:21]([O:13][CH2:12][CH2:11][O:10][CH:7]([CH3:9])[CH3:8])=[CH:20][C:16]=1[C:17]([OH:19])=[O:18]
Reactant: O=C(O)c1cc(F)ccc1Cl
Reactant: CC(C)OCCO
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CN1CCCC1=O
Solvent: O
Product: CC(C)OCCOc1ccc(Cl)c(C(=O)O)c1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
Under argon atmosphere, potassium tert-butoxide (168 mg) was added to a solution of 2-isopropoxyethanol (172 μL) in NMP (1.5 mL). The mixture was stirred at room temperature for 10 minutes, 2-chloro-5-fluorobenzoic acid (87 mg) was added, and it was then stirred at 130° C. for 4 hours. The reaction mixture was cooled on ice bath, water was added, and it was then acidified with 1N hydrochloric acid and extracted with ethyl acetate. The organic layer was separated, washed with brine, and dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain crude 2-chloro-5-[2-(propan-2-yloxy)ethoxy]benzoic acid. This was dissolved in DMF (2 mL), HATU (61 mg), N,N-diisopropylethylamine (29 μL) and 6-amino-N-(3-chloro-2-methylphenyl)-2-(methoxymethyl)-1H-benzimidazole-4-carboxamide (50 mg) were added in this order, and it was stirred at room temperature for 12 hours. The reaction mixture was poured into saturated aqueous sodium bicarbonate, and extracted with ethyl acetate. The organic layer was separated, washed sequentially with water and brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified on column chromatography to obtain N-(3-chloro-2-methylphenyl)-6-[({2-chloro-5-[2-(propan-2-yl oxy)ethoxy]phenyl}carbonyl)amino]-2-(methoxymethyl)-1H-benz imidazole-4-carboxamide (41 mg) as white powder. This was dissolved in ethyl acetate (2 mL), and treated with 4N hydrogen chloride/ethyl acetate (1.2 Eq). The precipitate was collected by filtration, and dried to obtain the titled compound (28 mg) as white powder.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:10])[CH3:9])=[CH:4][CH:3]=1.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C(N(CC)CC)C.[CH:30]([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=1[S:39][CH:40]([C:44](O)=[O:45])[C:41](O)=[O:42])([CH3:32])[CH3:31]>C(Cl)Cl>[OH:45][C:44]1[CH:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=2)[O:10][C:41](=[O:42])[C:40]=1[S:39][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][C:33]=1[CH:30]([CH3:32])[CH3:31]
Reactant: CC(=O)c1ccc(O)cc1
Reactant: CC(C)c1ccccc1SC(C(=O)O)C(=O)O
Agent: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)c1ccccc1Sc1c(O)cc(-c2ccc(O)cc2)oc1=O

Procedure:
The title compound was prepared by Method A using 4'-hydroxyacetophenone (0.657 g, 4.83 mmol), trimethylsilyl triflate (2.05 mL, 10.62 mmol), triethylamine (2.69 mL, 19.32 mmol), methylene chloride (20 mL), and diethyl ester of [(2-isopropylphenyl)thio]propanedioic acid (1.00 g, 3.22 mmol) m.p. 250° C.; (dec.) ; 1H NMR (400 MHz, DMSO-d6) δ 1.24 (d, 6H), 3.40 (m, 1H), 6.70 (s, 1H), 6.90 (t, 3H), 7.05 (t, 1H), 7.10 (t, 1H), 7.26 (d, 1H), 7.70 (d, 2H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:12])[CH:7]([NH2:11])[CH:8]([CH3:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.[O:19]([C:21]1[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1)[CH3:20].CCOC(C)=O.CCCCCC>C(#N)C>[C:1]([O:5][C:6](=[O:12])[CH:7]([NH:11][S:27]([C:24]1[CH:23]=[CH:22][C:21]([O:19][CH3:20])=[CH:26][CH:25]=1)(=[O:29])=[O:28])[CH:8]([CH3:9])[CH3:10])([CH3:2])([CH3:4])[CH3:3]
Reactant: COc1ccc(S(=O)(=O)Cl)cc1
Reactant: CC(C)C(N)C(=O)OC(C)(C)C
Solvent: CCOC(C)=O
Solvent: CC#N
Solvent: c1ccncc1
Product: COc1ccc(S(=O)(=O)NC(C(=O)OC(C)(C)C)C(C)C)cc1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a stirred suspension of 2-Amino-3-methyl-butyric acid tert-butyl ester (H-D-Val-OtBu.HCl) (500 mg, 2.38 mmol) in acetonitrile (20 ml) was added pyridine (767 μl, 9.52 mmol) at ambient temperature. A clear and colourless solution was quickly obtained. Then a solution of 4-methoxyl-benzenesulfonyl chloride (541 mg, 2.62 mmol) in acetonitrile (10 ml) was added dropwise and the mixture became slightly yellow coloured and was stirred at ambient temperature. TLC (EtOAc/Hexane, 1:1) monitoring showed the reaction was completed after 3 hours. After evaporation of acetonitrile, the residue was taken up in dichloromethane (30 ml) and extracted once each with 10% sodium bicarbonate solution (30 ml) and water (30 ml). Then the phases were separated and the dichloromethane phase was dried (Na2SO4), filtered and evaporated to afford the crude product. Flash chromatography using (Ethyl acetate/Hexane, 1:1) gave the pure product as a white solid. Yield 801 mg (93.90%).
Reaction SMILES: C[N:2](C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([S:20]([CH3:23])(=[O:22])=[O:21])[CH:15]=2)[N:8]=1)=O.[F:25][C:26]1[CH:31]=[CH:30][C:29]([NH:32]N)=[CH:28][CH:27]=1>>[F:25][C:26]1[CH:31]=[CH:30][C:29]([N:32]2[C:5]([C:7]3[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([S:20]([CH3:23])(=[O:22])=[O:21])[CH:15]=4)[N:8]=3)=[CH:4][CH:3]=[N:2]2)=[CH:28][CH:27]=1
Reactant: CN(C)/C=C/C(=O)c1nn(-c2cccc(S(C)(=O)=O)c2)ccc1=O
Reactant: NNc1ccc(F)cc1
Product: CS(=O)(=O)c1cccc(-n2ccc(=O)c(-c3ccnn3-c3ccc(F)cc3)n2)c1

Procedure:
Reaction of 3-((E)-3-dimethylamino-acryloyl)-1-(3-methansulfonyl-phenyl)-1H-pyridazin-4-one (A-7) and (4-fluoro-phenyl)-hydrazine according to example 43 gave the desired product. MS: M=411.2 (M+H)+
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][N:10]=[CH:11]2)=[CH:6][CH:5]=1)([O-])=O>CO.[Pd]>[CH:11]1[C:12]2[C:7](=[CH:6][CH:5]=[C:4]([NH2:1])[CH:13]=2)[CH:8]=[CH:9][N:10]=1
Reactant: O=[N+]([O-])c1ccc2ccncc2c1
Agent: [Pd]
Solvent: CO
Product: Nc1ccc2ccncc2c1
Temperature: 25 °C
Reaction time: 24.5 h
Yield: 90 %

Procedure:
To a suspend solution of Pd/C (10%, 100 mg) in methanol (20 mL) was added 31-3 (200 mg, 1.15 mmol) in methanol (40 mL). After having been degassed and recharged with hydrogen, the mixture was then stirred at room temperature for 24.5 h. TLC showed that the reaction was complete. The Pd/C was removed by filtration and the solvent was evaporated. The residual was used without further purification (150 mg, yield 90%).
Reaction SMILES: [CH2:1]1[O:10][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9].[NH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH2:18]>C(O)C>[CH2:17]([NH:18][CH2:1][CH:2]([OH:10])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][NH:11][CH2:1][CH:2]([OH:10])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: NCCCCCCN
Reactant: CCCCCCCC1CO1
Solvent: CCO
Product: CCCCCCCC(O)CNCCCCCCNCC(O)CCCCCCC

Procedure:
In a manner similar to that of Example 1, condensation of 1-nonene oxide (97.4 g.) and hexamethylenediamine (39.8 g.) and recrystallization of the resulting product (67 g.) from ethanol afforded N,N'-(1,6-hexylene)-bis[2-hydroxynonylamine] (I: R = CH3 (CH2)6, R' = H, X = (CH2)6, Z = H) (67 g., m.p. 122°-129.2° C.).
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[CH2:13][C@H:12]([O:14]C(=O)C)[CH:11]=[CH:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[OH-].[Li+].O.C(Cl)(Cl)Cl>C1COCC1.CO.O>[CH2:1]([O:8][C@@H:9]1[CH2:13][C@H:12]([OH:14])[CH:11]=[CH:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(=O)O[C@@H]1C=C[C@H](OCc2ccccc2)C1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: O[C@@H]1C=C[C@H](OCc2ccccc2)C1
Temperature: 25 °C
Reaction time: 2 h
Yield: 92.8 %

Procedure:
Dissolve (-)-acetic acid cis-4-benzyloxy-cyclopent-2-enyl ester (158 mg, 0.68 mmol, prepared in example 17) in THF/methanol/water (1.5/0.5/0.5 mL). Add lithium hydroxide monohydrate (0.75 mmol) with stirring. After stirring for about 2 hours at room temperature, dilute the reaction with water (10 mL) and extract with tert-butyl methyl ether. Combine the organic phases, dry over anhydrous magnesium sulfate, filter and concentrate under vacuum. Purify the residue by flash chromatography (silica gel, 2 g, 20% ethyl acetate/hexane, 1.5×2.5 cm column) to provide the title compound (120 mg, 92% yield), [α]20D =+5.0°, (c=0.93, chloroform).
Reaction SMILES: [C:1](OC)(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16].[H][H]>[Cr].[Cu]>[OH:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([O:17][CH3:18])=[O:16]
Reactant: COC(=O)CCCCCCCCCCCCCC(=O)OC
Reactant: [H][H]
Agent: [Cr]
Agent: [Cu]
Product: COC(=O)CCCCCCCCCCCCCCO
Reaction time: 2 h
Yield: 35 %

Procedure:
150 g (499 mmol) of dimethyl 1,15-pentadecandioate and 750 mg (0.5% by weight per the diester) of a commercial copper-chromium catalyst (content of copper as copper oxides: 42% by weight) were added to an autoclave and subjected to hydrogenation reaction at the hydrogen pressure of 20.0 Mpa at 280° C. After 2 hours, methyl 15-hydroxypentadecanoate was obtained in 35% yield. The degree of the conversion was 67% the selectivity was 53%, and the yield was 35%.