Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][N:3]=[C:2]1[NH2:6].N1C=CN=C1.[I-].[Li+].[CH2:14]([O:21][C:22]([NH:24][C@@H:25]([CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH2:41][CH2:42][CH2:43][C:44](OCC)=[O:45])=[CH:36][CH:35]=1)[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN(C)C=O>[CH2:14]([O:21][C:22]([NH:24][C@@H:25]([CH2:33][C:34]1[CH:39]=[CH:38][C:37]([O:40][CH2:41][CH2:42][CH2:43][C:44](=[O:45])[NH:6][C:2]2[NH:3][CH2:4][CH2:5][N:1]=2)=[CH:36][CH:35]=1)[C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])=[O:23])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: NC1=NCCN1
Reactant: CCOC(=O)CCCOc1ccc(C[C@H](NC(=O)OCc2ccccc2)C(=O)OC(C)(C)C)cc1
Agent: [I-]
Agent: [Li+]
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)[C@H](Cc1ccc(OCCCC(=O)NC2=NCCN2)cc1)NC(=O)OCc1ccccc1
Temperature: 40 °C
Reaction time: 4 h
Yield: 23.9 %

Procedure:
340 mg of 4,5-dihydro-1H-imidazol-2-ylamine, 13.6 mg of imidazole and 26.8 mg of lithium iodide were added to a solution of 970 mg of tert-butyl (2S)-2-benzyloxycarbonylamino-3-(4-(3-ethoxycarbonylpropyloxy)phenyl)propionate (Example 1a) in 5 ml of absolute dimethylformamide. The solution was stirred at 40° C. for 4 hours, an additional 170 mg of 4,5-dihydro-1H-imidazol-2-ylamine were added and the solution stirred at 55° C. for further 3 hours. After removal of the solvent in vacuo, the residue was treated with ethyl acetate, filtered, extracted with 10% strength aqueous KHCO3 solution, dried over MgSO4, filtered, concentrated in vacuo and precipitated with diisopropyl ether. The crude product was purified by silica gel chromatography (dichloromethane/methanol/glacial acetic acid 90/10/1). 250 mg of an amorphous product were obtained.
Reaction SMILES: Cl.Cl.[NH2:3][C:4]1[CH:5]=[C:6]([N:10]2[C:14]3[CH:15]=[CH:16][C:17]([C:19]([NH:21][CH2:22][C:23]4[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=4)=[O:20])=[CH:18][C:13]=3[N:12]=[CH:11]2)[CH:7]=[CH:8][CH:9]=1.[S:29]1[CH:33]=[CH:32][CH:31]=[C:30]1[S:34](Cl)(=[O:36])=[O:35]>N1C=CC=CC=1>[N:25]1[CH:26]=[CH:27][CH:28]=[C:23]([CH2:22][NH:21][C:19]([C:17]2[CH:16]=[CH:15][C:14]3[N:10]([C:6]4[CH:7]=[CH:8][CH:9]=[C:4]([NH:3][S:34]([C:30]5[S:29][CH:33]=[CH:32][CH:31]=5)(=[O:36])=[O:35])[CH:5]=4)[CH:11]=[N:12][C:13]=3[CH:18]=2)=[O:20])[CH:24]=1
Reactant: Nc1cccc(-n2cnc3cc(C(=O)NCc4cccnc4)ccc32)c1
Reactant: O=S(=O)(Cl)c1cccs1
Agent: Cl
Solvent: c1ccncc1
Product: O=C(NCc1cccnc1)c1ccc2c(c1)ncn2-c1cccc(NS(=O)(=O)c2cccs2)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
1-(3-Aminophenyl)-N-(pyridin-3-ylmethyl)-1H-benzimidazole-5-carboxamide dihydrochloride (60 mg, 0.17 mmol) was dissolved in 2 mL pyridine at 0° C. and 2-thiophenesulphonyl chloride (31 mg, 0.17 mmol) was added in one portion to the mixture, and the reaction was stirred room temperature. After 16 h, the reaction mixture was concentrated in vacuo. The residue was purified using the Waters mass-directed HPLC purification system to yield N-pyridin-3-ylmethyl-1-{3-[(thien-2-ylsulfonyl)amino]phenyl}-1H-benzimidazole-5-carboxamide as a white solid. 1H NMR (400 MHz, CD3OD): δ 8.60 (s, 1H), 8.48 (d, J=12.0 Hz, 2H), 8.30 (s, 1H), 7.90 (t, J=8.0 Hz, 2H), 7.69 (d, J=4.0 Hz, 1H), 7.55 (dd, J=1.2 Hz, 4.0 Hz, 1H), 7.48-7.43 (m, 3H), 7.37 (t, J=2.0 Hz, 1H), 7.21 (t, J=8.0 Hz, 1H), 7.09 (t, J=8.0 Hz, 1H), 4.67 (d, J=5.4 Hz, 2H). MS (ES+): m/z 490 [MH+].
Reaction SMILES: [CH2:1]([N:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][C:5](=O)[C:4]1=[O:14])[CH3:2].P(Br)(Br)([Br:17])=O.C(=O)([O-])[O-].[Na+].[Na+]>ClC(Cl)C>[Br:17][C:5]1[C:4](=[O:14])[N:3]([CH2:1][CH3:2])[C:12]2[C:7]([N:6]=1)=[CH:8][CH:9]=[CH:10][CH:11]=2
Reactant: CCn1c(=O)c(=O)[nH]c2ccccc21
Reactant: O=P(Br)(Br)Br
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(Cl)Cl
Product: CCn1c(=O)c(Br)nc2ccccc21
Reaction time: 2 h
Yield: 52.6 %

Procedure:
To 2 g (10.5 mM) of 1-ethyl-1,4-dihydroquinoxaline-2,3-dione in 20 ml of dichloroethane were added dropwise 3.16 g (11.0 mM) of POBr3. The reaction mixture was refluxed under stirring for 2 h and then treated with ice cold and an aqueous sodium carbonate solution. The mixture was filtered and the filtrate was extracted with dichloromethane, dried over anhydrous sodium sulfate and concentrated to give 1,4 g of 3-bromo-1-ethyl-quinoxalin-2(1H)-one as a yellow solid. Yield: 53%.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[Si](OCCC[C@H:33]1[O:37][C:36](=[O:38])[C@H:35]([S:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[C@H:34]1[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.S(=O)(O)[O-].[Na+].C(=O)(O)[O-].[Na+]>ClCCl.C(OCC)C>[O:38]=[C:36]1[CH:35]([S:39]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:9])[CH:34]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH2:33][O:37]1
Reactant: CC(C)(C)[Si](OCCC[C@H]1OC(=O)[C@H](Sc2ccccc2)[C@H]1c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CCOCC
Solvent: ClCCl
Product: O=C1OCC(c2ccccc2)C1S(=O)c1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
m-Chloroperbenzoic acid (242 mg) was added to a solution of (3R*,4S*,5R*)-5-[3-(t-butyldiphenylsilyloxy)propyl] -2-oxo-4-phenyl-3-phenylthiotetrahydrofuran in dichloromethane (10 ml) at 0° C. and the resulting mixture was stirred at 0° C. for 30 minutes. The resulting mixture was poured into a mixture of diethyl ether, aqueous sodium bisulfite and aqueous sodium bicarbonate. The organic layer was separated, washed with water and brine successively, dried over ( magnesium sulfate, and evaporated in vacuo to give (3R*,4S*,5R*)-5-[3-(t-butyldiphenylsilyloxy)propyl]-2(oxo-4-phenyl-3-phenylsulfinyltetrahydrofuran (537 mg) as an oil.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][N:5]([CH2:8][C:9]2([O:17][CH2:18][CH2:19][OH:20])[CH2:14][CH2:13][CH2:12][C:11]([CH3:16])([CH3:15])[CH2:10]2)[C:6]=1[CH3:7].[H-].[Na+].[CH3:23]I>CN(C)C=O.CCOCC>[Br:1][C:2]1[CH:3]=[N:4][N:5]([CH2:8][C:9]2([O:17][CH2:18][CH2:19][O:20][CH3:23])[CH2:14][CH2:13][CH2:12][C:11]([CH3:15])([CH3:16])[CH2:10]2)[C:6]=1[CH3:7]
Reactant: Cc1c(Br)cnn1CC1(OCCO)CCCC(C)(C)C1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: COCCOC1(Cn2ncc(Br)c2C)CCCC(C)(C)C1
Reaction time: 0.5 h

Procedure:
To a solution of EXAMPLE 180B (2.2 g) in N,N-dimethylformamide (20 mL) was added sodium hydride (0.38 g). After stirring for 30 minutes, methyl iodide (0.60 mL) was added. The reaction mixture was stirred for 2 hours at room temperature, diluted with ether (100 mL) and washed with water (2×75 mL) and brine (75 mL), dried over magnesium sulfate, filtered, and concentrated. Silica gel chromatography eluting with a gradient of 3% to 25% ethyl acetate/hexanes provided the title compound.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].C1COCC1.Cl[C:21]1[CH:26]=[CH:25][N:24]=[C:23]([C:27]([NH:29][CH3:30])=[O:28])[CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH3:30][NH:29][C:27]([C:23]1[CH:22]=[C:21]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=2)[CH:26]=[CH:25][N:24]=1)=[O:28]
Reactant: CNC(=O)c1cc(Cl)ccn1
Reactant: Nc1ccc(O)cc1
Agent: CC(C)(C)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CNC(=O)c1cc(Oc2ccc(N)cc2)ccn1
Temperature: 80 °C
Reaction time: 2 h
Yield: 98.3 %

Procedure:
To a solution of 4-aminophenol (1 g, 9.2 mmol) in DMF (20 mL) was added 1M potassium tert-butoxide in THF (9.7 mL, 9.7 mmol) at room temperature. After 2 h, (4-chloro(2-pyridyl))-N-methylcarboxamide (1.6 g, 9.2 mmol) and potassium carbonate (0.64 g, 4.6 mmol) were added and then the reaction mixture was heated to 80° C. for 6 h. After cooling, the reaction mixture was extracted with ethyl acetate (50 mL). The organic layer was washed with brine (20 mL), dried over magnesium sulfate. The solvent was removed in vacuo. The residue was purified by column chromatography to afford 4-(4-amino-phenoxy)-pyridine-2-carboxylic acid methylamide (2.2 g, 80%) as a light-brown solid. 1H NMR (400 MHz, DMSO-d6): δ 8.94 (s, 1H), 8.89 (s, 1H), 8.78 (q, J=5 Hz, 1H), 8.50 (d, J=6 Hz, 1H), 7.61-7.54 (m, 4H), 7.38 (d, J=3 Hz, 1H), 7.29 (d, J=9 Hz, 2H), 7.19-7.12 (m, 3H), 2.78 (d, J=5 Hz, 3H).
Reaction SMILES: C(N(C(C)C)C(C)C)C.I[C:11]1[CH:22]=[CH:21][C:14]([CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:13][CH:12]=1.[C:23]([C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33](=[O:36])[C:34]#[CH:35])=[CH:28][CH:27]=1)#[C:24][CH3:25]>[Cu]I>[C:23]([C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33](=[O:36])[C:34]#[C:35][C:11]2[CH:22]=[CH:21][C:14]([CH2:15][N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[CH:13][CH:12]=2)=[CH:28][CH:27]=1)#[C:24][CH3:25]
Reactant: C#CC(=O)Nc1ccc(C#CC)cc1
Reactant: Ic1ccc(CN2CCCC2)cc1
Agent: [Cu]I
Solvent: CCN(C(C)C)C(C)C
Product: CC#Cc1ccc(NC(=O)C#Cc2ccc(CN3CCCC3)cc2)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
10 mL of acetonitrile is degassed and combined with 0.35 mL (2 mmol) of ethyldiisopropylamine and 0.2 g (0.69 mmol) of 1-(4-iodobenzyl)pyrrolidine. Then the mixture is again degassed and 13 mg of copper (I) iodide, 34 mg of tetrakistriphenylphosphine palladium, and 137 mg (0.75 mmol) of propynoic acid-(4-prop-1-ynylphenyl)amide are then added in succession. The reaction mixture is stirred for 24 hours at ambient temperature and then combined with 60 mg of propynoic acid-(4-prop-1-ynylphenyl)amide. After 24 hours, the mixture is evaporated down. The purification is carried out by column chromatography on silica gel (dichloromethane/methanol/ammonia (30:1:0.1 to 20:1:0.1)). Yield: 24 mg (10% of theory); C23H22N2O (M=342.44); calc.: molecular ion peak (M+H)+: 343; found: molecular ion peak (M+H)+: 343; Rf value: 0.2 (silica gel, dichloromethane/methanol/ammonia=10:1:0.1).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1[NH2:11].[C:13]1([CH:23]=O)[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1[NH:11][CH2:23][C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1
Reactant: O=Cc1cccc2ccccc12
Reactant: COC(=O)c1cc(Cl)ccc1N
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: COC(=O)c1cc(Cl)ccc1NCc1cccc2ccccc12
Yield: 78 %

Procedure:
2-Amino-5-chlorobenzoic acid methyl ester (1.85 g, 10.0 mmol) was treated with 1-napthaldehyde (1.56 g, 10.0 mmol) and sodium triacetoxyborohydride (4.23 g, 20.0 mmol) in 1,2-dichloroethane as described in general procedure E to give 5-chloro-2-[(napthalen-1yl-methyl)-amino]-benzoic acid methyl ester (2.54 g, 78%). This methyl ester (2.0 g, 6.13 mmol) was treated with LiOH (2 eq, 1N aqueous solution) according to the general procedure C gave 5-chloro-2-[(napthalen-1yl-methyl)-amino]-benzoic acid (1.64 g, 86.0%).
Reaction SMILES: [CH3:1][N:2]([CH3:22])[C:3]([O:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([OH:19])[CH2:13][C:14](OCC)=[O:15])=[C:8]([CH:20]=[CH2:21])[CH:7]=1)=[O:4].[BH4-].[Li+].O.Cl>O1CCCC1>[CH3:22][N:2]([CH3:1])[C:3](=[O:4])[O:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([OH:19])[CH2:13][CH2:14][OH:15])=[C:8]([CH:20]=[CH2:21])[CH:7]=1
Reactant: C=Cc1cc(OC(=O)N(C)C)ccc1C(O)CC(=O)OCC
Agent: Cl
Agent: [BH4-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: C=Cc1cc(OC(=O)N(C)C)ccc1C(O)CCO
Temperature: 25 °C
Yield: 97.3 %

Procedure:
To a solution of ethyl 3-(4-dimethylcarbamoyloxy-2-vinyl-phenyl)-3-hydroxy-propionate (5.28 g, 17.2 mmol) obtained in step (d) of Example 192 in tetrahydrofuran (50 ml) was added lithium tetrahydroborate (544 mg, 25.0 mmol) at −20° C. with stirring, and the reaction temperature was raised gradually to ambient temperature over one hour under a nitrogen atmosphere. To the reaction mixture were added successively water (20 ml) and 1N hydrochloric acid (20 ml), and the resulting mixture was extracted with ethyl acetate (40 ml×2). The organic layer was dried over anhydrous sodium sulfate, filtered; and evaporated in vacuo to afford the crude product. The crude product was purified by chromatography on a silica gel column using mixed solvents of hexane and ethyl acetate (1:1-0:1) and ethyl acetate and methanol (5:1) successively as the eluents to afford the title compound (4.44 g, yield: 97%) as a colorless oil.
Reaction SMILES: [CH3:1][N:2]([CH3:25])[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[C:10]([CH3:12])[CH:9]=[CH:8][C:7]=1[NH:13][C:14]1[O:15][CH2:16][C:17](=[O:24])[C:18]=1[C:19]([O:21][CH2:22][CH3:23])=[O:20].[NH:26]1[C:34]2[C:29](=[CH:30][CH:31]=[CH:32][N:33]=2)[C:28]([CH:35]=O)=[CH:27]1.[OH-].[Na+]>C(O)C.Cl>[NH:26]1[C:34]2=[N:33][CH:32]=[CH:31][CH:30]=[C:29]2[C:28]([CH:35]=[C:16]2[O:15][C:14]([NH:13][C:7]3[CH:8]=[CH:9][C:10]([CH3:12])=[CH:11][C:6]=3[O:5][CH2:4][CH2:3][N:2]([CH3:1])[CH3:25])=[C:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[C:17]2=[O:24])=[CH:27]1
Reactant: CCOC(=O)C1=C(Nc2ccc(C)cc2OCCN(C)C)OCC1=O
Reactant: O=Cc1c[nH]c2ncccc12
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCOC(=O)C1=C(Nc2ccc(C)cc2OCCN(C)C)OC(=Cc2c[nH]c3ncccc23)C1=O
Yield: 5.5 %

Procedure:
To a stirred solution of ethyl 2-({2-[2-(dimethylamino)ethoxy]-4-methylphenyl}amino)-4-oxo-4,5-dihydrofuran-3-carboxylate (0.011 g, 0.030 mmol) which similarly prepared according to the procedure described in the Example 29, First step and 7-azaindole-3-carboxaldehyde (0.0044 g, 0.030 mmol) in ethanol (0.2 mL), 2M hydrochloric acid in ethanol (0.045 mL, 0.091 mmol) was added at ambient temperature. The mixture was refluxed for 9 h. Cooled with ice bath, 2M sodium hydroxide solution (0.041 mL, 0.082 mmol) was added dropwise to neutralize, and ethanol (0.5 mL) was added. The mixture was refluxed for further 16 min. The precipitate was collected by filtration, washed with hot ethanol. The solid was washed with hexane then dried to afford the titled compound as solid (0.00079 g, y. 5%).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([NH:19][C:20](=[O:31])[CH2:21][C:22]([NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:23])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16](I)[S:17][C:10]=12.Br[C:33]1[CH:38]=[CH:37][N+:36]([O-:39])=[CH:35][CH:34]=1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:3]=[C:4]([NH:19][C:20](=[O:31])[CH2:21][C:22](=[O:23])[NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:35]3[CH:34]=[CH:33][CH:38]=[CH:37][N+:36]=3[O-:39])[S:17][C:10]=12
Reactant: [O-][n+]1ccc(Br)cc1
Reactant: O=C(CC(=O)Nc1ccc(Oc2ccnc3cc(I)sc23)c(F)c1)Nc1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: O=C(CC(=O)Nc1ccc(Oc2ccnc3cc(-c4cccc[n+]4[O-])sc23)c(F)c1)Nc1ccccc1
Yield: 26.7 %

Procedure:
A solution of 411 (45 mg, 0.08 mmol), 4-bromopyridine N-oxide (250 mg, 1.43 mmol), bistrimethyltin (26 μL, 40 mg, 0.12 mmol) and Pd(PPh3)4 (10 mg, 0.01 mmol) in dioxane (1 mL) was heated to reflux for 4 hrs. The reaction mixture was cooled, concentrated and the residue was purified by flash chromatography using the gradient 5-10% MeOH in DCM as an eluent, to afford 409 (11 mg, 27% yield). 1H NMR δ (400 MHz, CD3OD): 8.71 (d, 1H, J=5.4 Hz), 8.6 (m, 3H), 8.04 (dd, 1H, J=2.4 Hz, J=12.3 Hz), 7.85 (t, 1H, J=8.4 Hz), 7.78 (m, 2H), 7.65 (m, 1H), 7.62 (m, 1H), 7.53 (m, 3H), 7.32 (t, 1H, J=7.4 Hz), 6.81 (d, 1H, J=5.5 Hz), 3.75 (s, 2H). MS (m/z: (M+1) 515.0 (100%).
Reaction SMILES: [CH3:1][CH:2]1[CH2:6][CH2:5][C:4](=[O:7])[N:3]1[C:8]1[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=1.[CH3:17][C:18]1[C:19]([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)=[N:20][CH:21]=[C:22]([CH3:24])[CH:23]=1>>[CH3:17][C:18]1[C:19]([N:25]2[CH2:26][CH2:27][N:28]([C:12]([C:11]3[CH:10]=[CH:9][C:8]([N:3]4[CH:2]([CH3:1])[CH2:6][CH2:5][C:4]4=[O:7])=[CH:16][CH:15]=3)=[O:14])[CH2:29][CH2:30]2)=[N:20][CH:21]=[C:22]([CH3:24])[CH:23]=1
Reactant: Cc1cnc(N2CCNCC2)c(C)c1
Reactant: CC1CCC(=O)N1c1ccc(C(=O)O)cc1
Product: Cc1cnc(N2CCN(C(=O)c3ccc(N4C(=O)CCC4C)cc3)CC2)c(C)c1
Yield: 51.8 %

Procedure:
Using 4-(2-methyl-5-oxopyrrolidin-1-yl)benzoic acid (438 mg) described in Preparation Example 50 and 1-(3,5-dimethylpyridin-2-yl)piperazine (383 mg) described in Preparation Example 79 and by the reaction and treatment in the same manner as in Example 93, the title compound (406 mg) was obtained.
Reaction SMILES: [Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1>C(Cl)Cl.[Cl-].[Na+].O.[Zn]>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: Clc1nc(Cl)c2ccccc2n1
Agent: [Cl-]
Agent: [Na+]
Agent: [Zn]
Solvent: ClCCl
Solvent: O
Product: Clc1ncc2ccccc2n1

Procedure:
A two-phase mixture of a solution of 2,4-dichloroquinazoline (5 g) in methylene chloride (100 mL) covered with 100 mL of saturated brine containing 9% NH4OH is treated with powdered zinc (5 g) and the resultant mixture is then refluxed for 4 h, cooled and filtered through celite. The organic layer is removed, diluted with ethyl acetate (100 ml), washed with 1 N HCl solution, dried and concentrated.
Reaction SMILES: F[C:2]1[N:7]=[C:6]([C:8]2[C:16]3[C:11](=[CH:12][N:13]=[C:14]([C:17]4[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=4)[CH:15]=3)[N:10](C3CCCCO3)[N:9]=2)[CH:5]=[CH:4][CH:3]=1.[NH:29]1[CH2:34][CH2:33][CH2:32][C@@H:31]([NH:35]C(=O)OCC2C=CC=CC=2)[CH2:30]1>>[N:19]1[CH:20]=[CH:21][CH:22]=[C:17]([C:14]2[CH:15]=[C:16]3[C:8]([C:6]4[N:7]=[C:2]([N:29]5[CH2:34][CH2:33][CH2:32][C@@H:31]([NH2:35])[CH2:30]5)[CH:3]=[CH:4][CH:5]=4)=[N:9][NH:10][C:11]3=[CH:12][N:13]=2)[CH:18]=1
Reactant: O=C(N[C@@H]1CCCNC1)OCc1ccccc1
Reactant: Fc1cccc(-c2nn(C3CCCCO3)c3cnc(-c4cccnc4)cc23)n1
Product: N[C@@H]1CCCN(c2cccc(-c3n[nH]c4cnc(-c5cccnc5)cc34)n2)C1
Yield: 15 %

Procedure:
Following the procedure of Example 144, 3-(6-fluoropyridin-2-yl)-5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine and (R)-benzyl piperidin-3-ylcarbamate were reacted to give 17 mg of 149 (15% over two steps). ESI MS m/z 372.1 (M+1). 1H NMR (400 MHz, DMSO): 14.24 (s, 1H), 9.49 (s, 1H), 9.30 (s, 1H), 9.10 (d, J=8.3 Hz, 1H), 9.06 (s, 1H), 8.36 (s, 3H), 8.21-8.12 (m, 1H), 7.78-7.72 (m, 1H), 7.56 (d, J=7.4 Hz, 1H), 6.99 (d, J=8.5 Hz, 1H), 4.49 (d, J=11.3 Hz, 2H), 3.53-3.44 (m, 3H), 3.35 (m, 1H), 3.22 (d, J=9.2 Hz, 1H), 2.10 (m, 1H), 1.95 (m, 1H)
Reaction SMILES: [CH3:1][O:2][C:3]1[C:33]([O:34][CH3:35])=[CH:32][C:6]2[CH2:7][C:8](=[O:31])[N:9]([CH2:12][CH2:13][CH2:14][N:15]([CH3:30])[CH:16]3[CH2:25][CH2:24][C:23]4[C:18](=[CH:19][C:20]([O:28][CH3:29])=[C:21]([O:26][CH3:27])[CH:22]=4)[CH2:17]3)[CH2:10][CH2:11][C:5]=2[CH:4]=1.[Se](=O)=[O:37].O>O1CCOCC1>[CH3:1][O:2][C:3]1[C:33]([O:34][CH3:35])=[CH:32][C:6]2[C:7](=[O:37])[C:8](=[O:31])[N:9]([CH2:12][CH2:13][CH2:14][N:15]([CH3:30])[CH:16]3[CH2:25][CH2:24][C:23]4[C:18](=[CH:19][C:20]([O:28][CH3:29])=[C:21]([O:26][CH3:27])[CH:22]=4)[CH2:17]3)[CH2:10][CH2:11][C:5]=2[CH:4]=1
Reactant: O=[Se]=O
Reactant: COc1cc2c(cc1OC)CC(=O)N(CCCN(C)C1CCc3cc(OC)c(OC)cc3C1)CC2
Solvent: O
Solvent: C1COCCO1
Product: COc1cc2c(cc1OC)CC(N(C)CCCN1CCc3cc(OC)c(OC)cc3C(=O)C1=O)CC2

Procedure:
Here, 1-[7,8-dimethoxy-1,3,4,5-tetrahydro-2H-3-benzazepin-2-on-3-yl]-3-[N-methyl-N-(6,7-dimethoxy-1,2,3,4-tetrahydronaphth-2-yl)-amino]-propane (1.64 g, 0.0034 mol) is added at 70° C. to a suspension of selenium dioxide (0.41 g, 0.0036 mol) and Celite (0.34 g) in 1,4-dioxan (17 ml) and water (0.68 ml) is added and the mixture is refluxed for 40 hours. After cooling, it is suction filtered, concentrated by rotary evaporation in vacuo and purified over silica gel (40 g) (32-63 μm) with methylene chloride and increasing amounts of ethanol (up to 40%). The clean fractions are concentrated by evaporation and the hydrochloride is precipitated from acetone. Yield: 0.6 g. Mp: >145° C. (decomp.).
Reaction SMILES: C(OC([N:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=2[O:20][CH:21]2[CH2:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]2=[N:30][OH:31])[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH:8]1[CH2:11][CH:10]([O:12][C:13]2[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:14]=2[O:20][CH:21]2[CH2:29][C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]2=[N:30][OH:31])[CH2:9]1
Reactant: CC(C)(C)OC(=O)N1CC(Oc2cc(Cl)ccc2OC2Cc3ccccc3C2=NO)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: ON=C1c2ccccc2CC1Oc1ccc(Cl)cc1OC1CNC1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
The title compound from Step B was dissolved in CH2Cl2 (20 mL), and CF3COOH (3 mL) was added. The mixture was stirred at 25° C. for 4 h. After concentration and purification via PTLC, the title compound was obtained (91 mg). MS (ESI): mass calcd. for C18H17ClN2O3, 344.1; m/z found, 345.0 [M+H]+. 1H NMR (MeOD): 8.40 (d, J=8.0 Hz, 1H), 7.50-6.80 (m, 6H), 5.48-5.46 (m, 1H), 5.18-5.10 (m, 1H), 4.45-4.32 (m, 2H), 4.18-4.08 (m, 2H), 3.62-3.52 (m, 1H), 3.16-3.08 (m, 1H).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:26])[N:10]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:11]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[CH:13]=2)=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:33](B(CC)CC)[CH3:34].O>CN(C)C=O>[CH2:33]([C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:26])[N:10]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:11]=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[CH:13]=2)=[CH:4][N:3]=1)[CH3:34]
Reactant: CCB(CC)CC
Reactant: O=c1c(-c2ccc(Cl)nc2)cc(-c2ccccn2)cn1-c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCc1ccc(-c2cc(-c3ccccn3)cn(-c3ccccc3)c2=O)cn1
Temperature: 100 °C
Reaction time: 1 h

Procedure:
13 mg of 3-(2-chloropyridin-5-yl)-5-(2-pyridyl)-1-phenyl-1,2-dihydropyridin-2-one was dissolved in 20 ml of dimethylformamide, followed by the addition of 10 mg of potassium carbonate and 2 mg of tetrakistriphenylphosphine palladium. Under stirring at room temperature in nitrogen atmosphere, triethylborane (1.0M tetrahydrofuran solution) was added dropwise thereinto, followed by heating under stirring at 100° C. for 1 hour in nitrogen atmosphere. After the reaction mixture was cooled to room temperature, water was added thereto, and extracted with ethyl acetate. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography (hexane/ethyl acetate system), to give 4 mg of the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[C:10]([C:12]([NH:14][C:15]2[CH:23]=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=2)=[O:13])[CH:9]=[C:8]2[C:4]=1[CH2:5][CH2:6][N:7]2[S:24]([C:27]1[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:28]=1[O:34][CH3:35])(=[O:26])=[O:25].CO[C:38]1C=CC(C)=C[C:39]=1S(Cl)(=O)=O>>[CH2:38]([O:20][C:19](=[O:21])[C:18]1[CH:17]=[CH:16][C:15]([NH:14][C:12]([C:10]2[CH:9]=[C:8]3[C:4]([CH2:5][CH2:6][N:7]3[S:24]([C:27]3[CH:32]=[C:31]([CH3:33])[CH:30]=[CH:29][C:28]=3[O:34][CH3:35])(=[O:26])=[O:25])=[C:3]([O:2][CH3:1])[CH:11]=2)=[O:13])=[CH:23][CH:22]=1)[CH3:39]
Reactant: COc1ccc(C)cc1S(=O)(=O)Cl
Reactant: COc1ccc(C)cc1S(=O)(=O)N1CCc2c(OC)cc(C(=O)Nc3ccc(C(=O)O)cc3)cc21
Product: CCOC(=O)c1ccc(NC(=O)c2cc(OC)c3c(c2)N(S(=O)(=O)c2cc(C)ccc2OC)CC3)cc1

Procedure:
4-{[4-Methoxy-1-(2-methoxy-5-methyl-benzenesulfonyl)-2,3-dihydro-1H-indole-6-carbonyl]-amino}-benzoic acid, m/z (ES+): 497.35 (M+H+.), was prepared in analogy to example 26, steps 1 to 6. Step 5 was performed using 2-methoxy-5-methyl-benzenesulfonyl chloride, yielding 4-{[4-methoxy-1-(2-methoxy-5-methyl-benzenesulfonyl)-2,3-dihydro-1H-indole-6-carbonyl]-amino}-benzoic acid ethyl ester, which was hydrolyzed in step 6.