Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si:1]([O:8][C@H:9]([CH2:43][O:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[CH2:10][N:11]([CH2:19][C@@H:20]1[CH2:29][CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[C:25]([C:30]3[CH:31]=[CH:32][C:33]4[C:38](=[O:39])[O:37][C:36](C)(C)[O:35][C:34]=4[CH:42]=3)[CH:26]=2)[O:21]1)[C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+]>CO>[C:14]([O:13][C:12]([N:11]([CH2:19][C@@H:20]1[CH2:29][CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[C:25]([C:30]3[CH:31]=[CH:32][C:33]([C:38]([O:37][CH3:36])=[O:39])=[C:34]([OH:35])[CH:42]=3)[CH:26]=2)[O:21]1)[CH2:10][C@H:9]([O:8][Si:1]([C:4]([CH3:5])([CH3:7])[CH3:6])([CH3:3])[CH3:2])[CH2:43][O:44][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)=[O:18])([CH3:15])([CH3:16])[CH3:17]
Reactant: CC(C)(C)OC(=O)N(C[C@@H]1CCc2cc(-c3ccc4c(c3)OC(C)(C)OC4=O)ccc2O1)C[C@@H](COc1ccccc1)O[Si](C)(C)C(C)(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: COC(=O)c1ccc(-c2ccc3c(c2)CC[C@@H](CN(C[C@@H](COc2ccccc2)O[Si](C)(C)C(C)(C)C)C(=O)OC(C)(C)C)O3)cc1O
Temperature: 25 °C
Reaction time: 18 h
Yield: 97 %

Procedure:
To a solution of Example 204 (0.8 g, 1.14 mmol, 1.0 eq.) in methanol (10 mL) was added potassium carbonate (0.078 g, 0.57 mmol, 0.5 eq.) at room temperature. The reaction mixture was allowed to stir at room temperature for 18 hours and then concentrated under reduced pressure. The resulting residue was washed with distilled water (10 mL) and extracted with ethyl acetate (3×10 mL). The combined extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford the desired product as pale yellow oil (0.75 g, 97%). 1H NMR (CDCl3) δ10.68 (s, 1 H), 7.73 (d, 1H), 7.26-7.14 (m, 4H), 6.94 (dd, 1H), 6.86-6.75 (m, 5H), 4.21-4.02 (m, 2H), 3.83 (s, 3H), 3.80-3.56 (m, 4H), 3.40-3.21 (m, 2H), 2.80-2.67 (m, 2H), 1.95-1.92 (m, 1H), 1.65-1.60 (m, 1H), 1.38 (s, 9H), 0.83 (s, 9H), 0.001 (s, 6H).
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[C@@H:4]2[CH2:5][C:6]3[C:10]([C@H:3]12)=[C:9]([CH3:11])[S:8][C:7]=3[C:12]([OH:14])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(C(C)C)C(C)C)C.Cl.[NH2:48][CH2:49][C:50]1[CH:55]=[CH:54][C:53]([OH:56])=[C:52]([CH3:57])[CH:51]=1>CN(C=O)C.C(O)=O>[OH:56][C:53]1[CH:54]=[CH:55][C:50]([CH2:49][NH:48][C:12]([C:7]2[S:8][C:9]([CH3:11])=[C:10]3[C:6]=2[CH2:5][C@H:4]2[C:2]([CH3:1])([CH3:15])[C@H:3]23)=[O:14])=[CH:51][C:52]=1[CH3:57]
Reactant: Cc1sc(C(=O)O)c2c1[C@H]1[C@@H](C2)C1(C)C
Reactant: Cc1cc(CN)ccc1O
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cl
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: O=CO
Product: Cc1cc(CNC(=O)c2sc(C)c3c2C[C@@H]2[C@H]3C2(C)C)ccc1O
Reaction time: 0.33 h
Yield: 50.4 %

Procedure:
A solution of (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid (111 mg, 0.50 mmol), TBTU (177 mg, 0.55 mmol) and ethyl-diisopropylamine (282 μL, 1.65 mmol) in DMF (15 mL) is allowed to stand at rt for 20 min. A solution of 4-aminomethyl-2-methyl-phenol hydrochloride (96 mg, 0.55 mmol) and ethyl-diisopropylamine (94 μL, 0.55 mmol) in DMF (1.5 mL) is added and the mixture is allowed to stand at rt for 3 h. After the addition of formic acid (0.2 mL), the mixture is separated by HPLC to afford (1aS,5aR)-1,1,2-trimethyl-1,1a,5,5a-tetrahydro-3-thia-cyclopropa[a]pentalene-4-carboxylic acid 4-hydroxy-3-methyl-benzylamide (86 mg) as a colourless oil. LC-MS: tR=0.99 min, [M+1]+=342.17.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[CH3:10].C1C(=O)N([Br:18])C(=O)C1>C(Cl)(Cl)(Cl)Cl>[Br:18][CH2:10][C:3]1[CH:4]=[C:5]([O:8][CH3:9])[CH:6]=[CH:7][C:2]=1[F:1]
Reactant: O=C1CCC(=O)N1Br
Reactant: COc1ccc(F)c(C)c1
Solvent: ClC(Cl)(Cl)Cl
Product: COc1ccc(F)c(CBr)c1
Temperature: 25 °C
Yield: 95.8 %

Procedure:
To a solution of 1-fluoro-4-methoxy-2-methylbenzene (2.0 g, 14.29 mmol) in CCl4, NBS (2.55 g, 14.29 mmol) and PhCO3H (80 mg) were added. The reaction mixture was heated at reflux for 2 h, cooled to room temperature, and the solid was filtered off. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (eluting with PE/EA=20/1) to give the target compound (3.0 g) as an oil. 1H NMR (CDCl3): δ 6.97-6.83 (m, 3H), 4.48 (s, 2H), 3.78 (s, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.[C:10]([CH2:14][C:15](OC)=[O:16])(=O)[CH2:11][CH3:12].O>C1C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:11]([C:10]1[NH:1][C:2]2[C:7]([C:15](=[O:16])[CH:14]=1)=[N:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=2)[CH3:12]
Reactant: CCC(=O)CC(=O)OC
Reactant: COc1ccc(N)cn1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Solvent: O
Product: CCc1cc(=O)c2nc(OC)ccc2[nH]1
Yield: 39.3 %

Procedure:
A solution of 5-amino-2-methoxypyridine (50 g), methyl propionylacetate (57.3 g) and p-toluenesulphonic acid (0.5 g) in benzene (200 ml) was heated under reflux with azeotropic removal of water for 20 hours. Volatile material was removed by evaporation and the residue added to a refluxing eutectic mixure of 26.5% v/v diphenyl and 73.5% v/v diphenyl oxide (140 ml). The solution was heated under reflux for 1 hour, cooled and diluted with hexane (500 ml). The precipitated solid was filtered off and triturated with hot methanol (500 ml) to give 2-ethyl-6-methoxy-1,5-naphthyridin-4(1H)-one (E5) (32.3 g), as a pale brown solid, m.p. 279°-281° C.; NMR (d6 -DMSO): 1.2(t,3H), 2.65(q,2H), 3.95(s,3H), 6.3(br s, 1H), 7.15(d,1H), 7.95(d,1H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10](=[O:28])[CH:11]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:12][CH:13]=[CH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[CH:16]=2)=[CH:4][CH:3]=1.[C:29]([O:33]C)(=[O:32])[CH:30]=[CH2:31]>CO.C(COC)OC>[CH3:21][C:17]1[CH:16]=[C:15]([CH:20]=[CH:19][CH:18]=1)[CH:14]=[CH:13][CH2:12][C:11]([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([C:10](=[O:28])[CH:9]=[CH:8][C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[CH2:31][CH2:30][C:29]([OH:33])=[O:32]
Reactant: C=CC(=O)OC
Reactant: Cc1cccc(C=CCC(C(=O)C=Cc2ccc(Cl)cc2)c2ccccc2)c1
Solvent: COCCOC
Solvent: CO
Product: Cc1cccc(C=CCC(CCC(=O)O)(C(=O)C=Cc2ccc(Cl)cc2)c2ccccc2)c1
Reaction time: 96 h

Procedure:
Triton B (2 ml., 40% in MeOH) is added to a stirred solution of 1-(p-chlorophenyl)-4-phenyl-7-(m-methylphenyl)-1,6-heptadien-3-one (19.33 g., 0.05 mole) in glyme (250 ml.) followed by the addition of methyl acrylate (4.73 g., 0.055 mole) in glyme (50 ml.). The solution is stirred for 96 hours and the solvent is removed under reduced pressure. The residue is suspended in methanol (700 ml.) and a 20% sodium hydroxide solution (35 ml.) is added. After an additional 24 hours, the methanol is evaporated in vacuo and the residue is dissolved in water. Extraction with ether removes unreacted ketone. The aqueous solution is acidified and the solid that separates is collected, washed well with water, and air-dried, yield 9.78 g., m.p. 135°-144°C. Recyrstallization from butyl chloride produces material with m.p. 154°-155°C.
Reaction SMILES: C([O:9][CH2:10][CH2:11][CH2:12][N:13]1[C:21]2[C:16](=[CH:17][C:18]([CH2:24][C@H:25]([NH:27][CH2:28][CH2:29][O:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[O:37][CH2:38][CH3:39])[CH3:26])=[CH:19][C:20]=2[C:22]#[N:23])[CH2:15][CH2:14]1)(=O)C1C=CC=CC=1.[OH-].[K+]>CO.O>[CH2:38]([O:37][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=1[O:30][CH2:29][CH2:28][NH:27][C@H:25]([CH3:26])[CH2:24][C:18]1[CH:17]=[C:16]2[C:21](=[C:20]([C:22]#[N:23])[CH:19]=1)[N:13]([CH2:12][CH2:11][CH2:10][OH:9])[CH2:14][CH2:15]2)[CH3:39]
Reactant: CCOc1ccccc1OCCN[C@H](C)Cc1cc(C#N)c2c(c1)CCN2CCCOC(=O)c1ccccc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CCOc1ccccc1OCCN[C@H](C)Cc1cc(C#N)c2c(c1)CCN2CCCO
Yield: 104.4 %

Procedure:
(R)-3-[7-Cyano-5-[2-[[2-(2-ethoxyphenoxy)ethyl]-amino]propyl]-2,3-dihydro-1H-indol-1-yl]propyl benzoate (7.23 g) was dissolved in methanol (46 ml) and the solution was added to a solution of potassium hydroxide (1.54 g) in distilled water (9.2 ml). After being heated under reflux for 1 hour, the reaction mixture was concentrated in vacuo. Distilled water (100 ml) was added to the residue and the resulting mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous sodium bicarbonate solution and brine, and dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was dissolved in toluene(30 ml) and the toluene was removed in vacuo to give (R)-5-[2-[[2-(2-ethoxyphenoxy)ethyl]amino]propyl]-1-(3-hydroxypropyl)-2,3-dihydro-1H-indole-7-carbonitrile(6.06 g) as a pale brown oil.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[O:3][C:4]1[CH:5]=[C:6]([CH2:10][NH2:11])[CH:7]=[CH:8][CH:9]=1.[F:14][C:15]([F:20])([F:19])[CH:16]1[O:18][CH2:17]1>>[F:1][C:2]([F:12])([F:13])[O:3][C:4]1[CH:5]=[C:6]([CH2:10][NH:11][CH2:17][CH:16]([OH:18])[C:15]([F:20])([F:19])[F:14])[CH:7]=[CH:8][CH:9]=1
Reactant: FC(F)(F)C1CO1
Reactant: NCc1cccc(OC(F)(F)F)c1
Product: OC(CNCc1cccc(OC(F)(F)F)c1)C(F)(F)F
Temperature: 80 °C
Reaction time: 1.5 h
Yield: 36.8 %

Procedure:
EX-632A) 3-Trifluoromethoxybenzenemethanamine (1.15g, 6 mmol) and 1,1,1-trifluoro-2,3-epoxypropane (0.67 g, 6 mmol) were combined and stirred at 80° C. for 1.5 h. The mixture was cooled to room temperature, and the resulting solid was recrystallized from hot hexanes. The white solid was isolated by vacuum filtration and washed with cold hexanes to give 0.67 g (37%) of pure 3-[[[3-(trifluoromethoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol. 1H NMR (CDCl3) δ 7.37 (t, 1H), 7.24 (d, 1H), 7.15 (m, 2H), 3.99 (m, 1H), 3.85 (d, 2H), 2.98 (dd, 1H), 2.88 (dd, 1H), 2.79 (s, 1H). 19F NMR (CDCl3) δ −58.19 (s, 3F), −78.88 (s, 3F). HRMS calcd. for C11H11F6NO2: 304.0772 [M+H]+, found: 304.0794.
Reaction SMILES: F[C:2]1[N:11]=[CH:10][C:9]2[C:8]([NH:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Br:19])[CH:14]=3)=[N:7][CH:6]=[N:5][C:4]=2[CH:3]=1.[CH2:20]([N:22](CC)CC)C.Cl.CN>C(O)(C)C>[Br:19][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=1)[NH:12][C:8]1[C:9]2[CH:10]=[N:11][C:2]([NH:22][CH3:20])=[CH:3][C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: Fc1cc2ncnc(Nc3cccc(Br)c3)c2cn1
Reactant: CCN(CC)CC
Agent: CN
Agent: Cl
Solvent: CC(C)O
Product: CNc1cc2ncnc(Nc3cccc(Br)c3)c2cn1
Temperature: 95 °C
Reaction time: 5 h
Yield: 65.8 %

Procedure:
A mixture of 7-fluoro-4-(3-bromoanilino)pyrido[4,3-d]pyrimidine (74 mg, 0.23 mmol), triethylamine (7 mL, 50 mmol) and methylamine hydrochloride (3.0 g, 44 mmol) in isopropanol (30 mL) contained in a steel bomb is stirred at 95° C. (oil bath) for 5 h. The resulting mixture is concentrated under vacuum, basified with aqueous Na2CO3, diluted with water and extracted with EtOAc (3×100 mL). Chromatography of this extract on silica gel (3% MeOH/CH2Cl2) gives 4-(3-bromoanilino)-7-methylaminopyrido[4,3-d]pyrimidine (50 mg, 65%) as a pale yellow solid. 1H NMR (DMSO) δ 9.93 (1H, brs), 9.37 (1H, s), 8.47 (1H, s), 8.18 (1H, s), 7.84 (1H, d, J=7.8 Hz), 7.34 (1H, t, J=7.9 Hz), 7.30 (1H, brd, J=8.1 Hz), 7.19 (1H, q, J=4.7 Hz), 6.35 (1H, s), 2.85 (3H, d, J=4.8 Hz).
Reaction SMILES: [C:1](=[O:29])([O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:15]=2[F:22])=[C:10]([C:23]#[C:24][C:25]([OH:28])([CH3:27])[CH3:26])[CH:9]=1)[O:2][C:3]([CH3:6])([CH3:5])[CH3:4].I[CH3:31]>C1(C)C=CC=CC=1.[Ag-]=O.[Ag+]>[C:1](=[O:29])([O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:15]=2[F:22])=[C:10]([C:23]#[C:24][C:25]([O:28][CH3:31])([CH3:27])[CH3:26])[CH:9]=1)[O:2][C:3]([CH3:6])([CH3:5])[CH3:4]
Reactant: COc1ccc(F)c(-c2ccc(OC(=O)OC(C)(C)C)cc2C#CC(C)(C)O)c1
Reactant: CI
Agent: O=[Ag-]
Agent: [Ag+]
Solvent: Cc1ccccc1
Product: COc1ccc(F)c(-c2ccc(OC(=O)OC(C)(C)C)cc2C#CC(C)(C)OC)c1
Temperature: 40 °C
Reaction time: 20 h

Procedure:
To a solution of tert-butyl 2′-fluoro-2-(3-hydroxy-3-methylbut-1-yn-1-yl)-5′-methoxybiphenyl-4-yl carbonate (314 mg) and iodomethane (0.50 mL) in toluene (5 mL) was added silver(I) oxide (365 mg). After stirring at 40° C. for 20 hr, silver(I) (365 mg) was added to the reaction mixture. The mixture was stirred at 40° C. for 70 hr. The reaction mixture was filtered, the solvent of the filtrate was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (244 mg) as a colorless oil.
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]([NH:6][CH:7]([C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:5].[C:21](O)(=[O:28])[C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1>>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([CH:7]([NH:6][C:4]([CH2:3][NH:2][C:21](=[O:28])[C:22]2[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=2)=[O:5])[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:15][CH:16]=1
Reactant: NCC(=O)NC(c1ccccc1)c1ccc(Cl)cc1
Reactant: O=C(O)c1ccncc1
Agent: Cl
Product: O=C(CNC(=O)c1ccncc1)NC(c1ccccc1)c1ccc(Cl)cc1

Procedure:
Prepared in analogy to example 1.12 from rac-2-amino-N-[(4-chloro-phenyl)-phenyl-methyl]-acetamide hydrochloride (Example 3.1) and isonicotinic acid.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[O:12].[H-].[Na+].Br[CH2:16][CH2:17][Cl:18]>CN(C)C=O>[Cl:18][CH2:17][CH2:16][N:7]1[C:8]2[C:4](=[CH:3][C:2]([F:1])=[CH:10][CH:9]=2)[C:5](=[O:12])[C:6]1=[O:11]
Reactant: ClCCBr
Reactant: O=C1Nc2ccc(F)cc2C1=O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C1C(=O)N(CCCl)c2ccc(F)cc21
Temperature: 0 °C

Procedure:
5-Fluoro-1H-indole-2,3-dione was dissolved in dimethylformamide. Sodium hydride (60% dispersion in mineral oil)(1.2 equivalents) was added in portions with stirring and cooling (ice-water bath) and the mixture was stirred until gas evolution ceased. 1-Bromo-2-chloroethane (1.2 equivalents) was added dropwise. The mixture was stirred at room temperature for 24 hours and then quenched into water and extracted into chloroform. The combined organic phases were washed with water, dried (MgSO4), filtered and concentrated under reduced pressure. The resulting oil was purified by chromatography on silica gel, eluent chloroform, to give 1-(2-chloro-1-ethyl)-5-fluoro-1H-indole-2,3-dione as a red solid.
Reaction SMILES: C([N:8]1[C:13](=[O:14])[C:12]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[C:11]([C:22]2[CH:27]=[CH:26][C:25]([S:28]([NH2:31])(=[O:30])=[O:29])=[CH:24][CH:23]=2)[CH:10]=[N:9]1)C1C=CC=CC=1.[F:32][C:33]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:34]=1[CH2:35]Br>>[F:32][C:33]1[CH:40]=[C:39]([F:41])[CH:38]=[CH:37][C:34]=1[CH2:35][N:8]1[C:13](=[O:14])[C:12]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[C:11]([C:22]2[CH:27]=[CH:26][C:25]([S:28]([NH2:31])(=[O:30])=[O:29])=[CH:24][CH:23]=2)[CH:10]=[N:9]1
Reactant: NS(=O)(=O)c1ccc(-c2cnn(Cc3ccccc3)c(=O)c2-c2ccc(F)cc2)cc1
Reactant: Fc1ccc(CBr)c(F)c1
Product: NS(=O)(=O)c1ccc(-c2cnn(Cc3ccc(F)cc3F)c(=O)c2-c2ccc(F)cc2)cc1
Yield: 24 %

Procedure:
2-Benzyl-4-(4-fluorophenyl)-5-[4-(aminosulfonyl)phenyl]-3(2H)-pyridazinone, prepared according to the method of Example 68, was N-debenzylated according to the method of Example 11. The intermediate was N-alkylated according to the method of Example 20, substituting 2,4-difluorobenzylbromide in place of 4-fluorobenzyl bromide to provide the title compound (yield: 65 mg, 24%). mp 236-238° C. 1H NMR (300 MHz, CDCl3) δ 4.78 (s, 2H), 5.43 (s, 2H), 6.88 (m, 2H), 6.97 (t, J=9 Hz, 2H), 7.18 (dd, J=9 Hz, 6 Hz, 2H), 7.38 (d, J=9 Hz, 2H), 7.55 (m, 1H), 7.85 (s, 1H), 7.86 (d, J=9 Hz, 2H). MS (DCI/NH3) m/z 472 (M+H)+. Anal. calc. for C23H16F3N3O3S: C, 58.59; H, 3.42; N, 8.91. Found: C, 58.44; H, 3.47; N, 8.72.
Reaction SMILES: [O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[CH:12]=[C:11]([CH3:13])[C:10]([C:14]3[CH:15]=[CH:16][C:17]4[C:18]5[N:38]([CH:39]6[CH2:44][CH2:43][O:42][CH2:41][CH2:40]6)[N:37]=[CH:36][C:19]=5[C:20](=[O:35])[N:21](CC5C=CC(OC)=CC=5OC)[C:22]=4[CH:23]=3)=[C:9]([CH3:45])[CH:8]=2)[CH2:3][CH2:2]1.C1COCC1.[H][H]>C(O)C.[C].[Pd]>[CH3:13][C:11]1[CH:12]=[C:7]([CH:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)[CH:8]=[C:9]([CH3:45])[C:10]=1[C:14]1[CH:15]=[CH:16][C:17]2[C:18]3[N:38]([CH:39]4[CH2:44][CH2:43][O:42][CH2:41][CH2:40]4)[N:37]=[CH:36][C:19]=3[C:20](=[O:35])[NH:21][C:22]=2[CH:23]=1
Reactant: COc1ccc(Cn2c(=O)c3cnn(C4CCOCC4)c3c3ccc(-c4c(C)cc(C5=CCOCC5)cc4C)cc32)c(OC)c1
Reactant: [H][H]
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: Cc1cc(C2CCOCC2)cc(C)c1-c1ccc2c(c1)[nH]c(=O)c1cnn(C3CCOCC3)c12
Temperature: 60 °C
Reaction time: 14 h
Yield: 44.5 %

Procedure:
10% palladium carbon (50% wet, 15 mg) was added to a solution of 7-[4-(3,6-dihydro-2H-pyran-4-yl)-2,6-dimethylphenyl]-5-(2,4-dimethoxybenzyl)-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]quinolin-4(5H)-one (44 mg) in ethanol (2 mL)-THF (2 mL). The reaction mixture was stirred at mom temperature for four hours and 35 minutes in a hydrogen atmosphere. The catalyst was removed from the reaction mixture by filtration, and the filtrate was then concentrated under reduced pressure. TFA (1.5 mL) was added to the resulting residue. The reaction mixture was stirred at 60° C. for 14 hours. The reaction mixture was returned to room temperature, and the reaction mixture was then concentrated under reduced pressure. Chloroform and a saturated aqueous sodium bicarbonate solution were added to the residue, and the organic layer was separated. The aqueous layer was re-extracted with chloroform. The combined organic layers were dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform 100%, then ethyl acetate 100%). The target fraction was collected and concentrated. Ethyl acetate and MTBE were added to the resulting residue. The precipitated solid was collected by filtration and dried under reduced pressure to give the title compound (14.8 mg).
Reaction SMILES: Cl[CH:2]1[C:8](=[O:9])[NH:7][C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[N:4]([CH3:14])[CH2:3]1.[C:15]1(=[O:25])[NH:19][C:18](=[O:20])[C:17]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:16]12.[K]>O>[C:15]1(=[O:25])[N:19]([CH:2]2[C:8](=[O:9])[NH:7][C:6]3[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=3[N:4]([CH3:14])[CH2:3]2)[C:18](=[O:20])[C:17]2=[CH:21][CH:22]=[CH:23][CH:24]=[C:16]12
Reactant: CN1CC(Cl)C(=O)Nc2ccccc21
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: O
Product: CN1CC(N2C(=O)c3ccccc3C2=O)C(=O)Nc2ccccc21
Reaction time: 1 h

Procedure:
A mixture of 1.05 g of 3-chloro-5-methyl-1,3,4,5-tetrahydro-1,5-benzodiazepin-2-one and 1.0 of potassium phthalimide is warmed to 90° overnight. The reaction mixture is poured into 20 ml of water and stirring is continued for 1 hr. Isolation and drying affords 3-phthalimido-5-methyl-1,3,4,5-tetrahydro-1,5-benzodiazepin-2-one.
Reaction SMILES: [H-].[Na+].[Cl:3][C:4]1[CH:19]=[CH:18][C:7]2[NH:8][C:9](=[O:17])[N:10]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)[C:6]=2[CH:5]=1.[CH3:20][O:21][C:22]1[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=[CH:24][C:23]=1[S:31](Cl)(=[O:33])=[O:32].O>CN(C=O)C>[Cl:3][C:4]1[CH:19]=[CH:18][C:7]2[N:8]([S:31]([C:23]3[CH:24]=[CH:25][C:26]([N+:28]([O-:30])=[O:29])=[CH:27][C:22]=3[O:21][CH3:20])(=[O:32])=[O:33])[C:9](=[O:17])[N:10]([CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]3)[C:6]=2[CH:5]=1
Reactant: O=c1[nH]c2ccc(Cl)cc2n1C1CCCCC1
Reactant: COc1cc([N+](=O)[O-])ccc1S(=O)(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc([N+](=O)[O-])ccc1S(=O)(=O)n1c(=O)n(C2CCCCC2)c2cc(Cl)ccc21
Temperature: 25 °C
Reaction time: 4 h

Procedure:
0.13 g of sodium hydride as an 80% dispersion in oil was added in portions, with stirring, to a solution of 1 g of 5-chloro-3-cyclohexyl-1,3-dihydro-2H-benzimidazol-2-one in 10 ml of DMF at room temperature; 1.1 g of 2-methoxy-4-nitrobenzenesulfonyl chloride were then introduced and the reaction medium was stirred at room temperature for 4 hours. The solvent was then evaporated off under vacuum and the residue obtained was taken up with water. It was then extracted with DCM, washed with water and then dried over sodium sulfate and the solvent was evaporated off to dryness. The residue obtained was chromatographed on silica using a DCM/AcOEt mixture (95/5; v/v) as the eluent to give the expected product in the form of a slightly yellow solid, which crystallized from absolute EtOH. m=1.52 g. M.p.=185° C.
Reaction SMILES: Br.[CH3:2][N:3]1[N:7]=[N:6][C:5]([C:8]2[CH2:9][NH:10][CH2:11][CH2:12][CH:13]=2)=[N:4]1.[CH:14](O)=O>C=O>[CH3:2][N:3]1[N:7]=[N:6][C:5]([C:8]2[CH2:9][N:10]([CH3:14])[CH2:11][CH2:12][CH:13]=2)=[N:4]1
Reactant: Cn1nnc(C2=CCCNC2)n1
Reactant: O=CO
Agent: Br
Agent: C=O
Product: CN1CCC=C(c2nnn(C)n2)C1
Yield: 74 %

Procedure:
A solution of 8 (0.70 g, 0.0028 mol) in formic acid (20 ml) and 35% formaldehyde (7 ml) was refluxed overnight. The solution was evaporated in vacuo, and the residue was taken up in ether (20 ml) and 28% sodium hydroxide (20 ml). The phases were separated, and the aqueous phase was extracted three times with dichloromethane (20 ml). The combined organic phases were washed four times with saturated sodium chdloride solution (20 ml). The organic phase was dried over magnesium sulphate and evaporated in vacuo yielding 0.60 g or crude 10. Crystallization from ether-light petroleum gave 0.37 g (0.0021 mol, 74%) of title compound, M.P. 86°-87° C. Anal. (C8H13N5) C, H, N.