Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2([C:18]3[CH:23]=[CH:22][N:21]=[CH:20][C:19]=3[F:24])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]([NH2:17])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[F:25][C:26]1[CH:27]=[N:28][CH:29]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:31]=1>>[F:24][C:19]1[CH:20]=[N:21][CH:22]=[CH:23][C:18]=1[C:8]1([C:16]2[CH:11]=[CH:12][CH:13]=[C:14]([C:30]3[CH:29]=[N:28][CH:27]=[C:26]([F:25])[CH:31]=3)[CH:15]=2)[C:4]2[C:5](=[CH:6][CH:7]=[CH:2][CH:3]=2)[C:10]([NH2:17])=[N:9]1
Reactant: CC1(C)OB(c2cncc(F)c2)OC1(C)C
Reactant: NC1=NC(c2cccc(Br)c2)(c2ccncc2F)c2ccccc21
Product: NC1=NC(c2cccc(-c3cncc(F)c3)c2)(c2ccncc2F)c2ccccc21
Yield: 57 %

Procedure:
The title compound was synthesized from 1-(3-bromophenyl)-1-(3-fluoropyridin-4-yl)-1H-isoindol-3-amine (Scheme #12, I) as described in Scheme #10, D in 57% yield using 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine. 1H NMR (DMSO-d6) δ 8.58-8.52 (m, 1 H), 8.49 (d, J=2.78 Hz, 1 H), 8.37 (d, J=2.78 Hz, 1 H), 8.27 (d, J=4.80 Hz, 1 H), 7.88-7.82 (m, 1 H), 7.81-7.72 (m, 2 H), 7.60-7.53 (m, 1 H), 7.51-7.40 (m, 3 H), 7.35 (t, J=7.71 Hz, 1 H), 7.30-7.25 (m, 1 H), 7.21 (dd, J=6.82, 5.05 Hz, 1 H), 6.95 (br s, 2 H), 1.84 (s, 1.4 H); MS (ESI) m/z 399 [M+1]+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:11][CH:10]2[O:22][CH2:23][CH2:24][O:25]S(C2C=CC(C)=CC=2)(=O)=O)=[CH:5][CH:4]=1.O[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][C:38]=1[CH2:43][CH2:44][NH:45][C:46](=[O:48])[CH3:47]>>[C:46]([NH:45][CH2:44][CH2:43][C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][C:37]=1[O:25][CH2:24][CH2:23][O:22][CH:10]1[CH:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:11]1)(=[O:48])[CH3:47]
Reactant: COc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCCOS(=O)(=O)c2ccc(C)cc2)cc1
Reactant: CC(=O)NCCc1ccccc1O
Product: COc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCCOc2ccccc2CCNC(C)=O)cc1

Procedure:
Analogously to Method G, 0.24 g of tertbutyl 4-(4-methoxyphenyl)-3-[2-(toluene-4-sulphonyloxy)ethoxy]piperidine-1-carboxylate and 0.17 g of N-[2-(2-hydroxyphenyl)ethyl]acetamide are reacted. The title compound is obtained as an orange oil. Rf=0.50 (200:20:1 dichloromethane-methanol-25% conc. ammonia); Rt=4.85.
Reaction SMILES: [C:1]([O:4][C:5]1[C:6](=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:7]([OH:9])=[O:8])(=[O:3])[CH3:2].Cl[CH2:15][C:16]([N:18]([CH2:21][CH3:22])[CH2:19][CH3:20])=[O:17].C(N(CC)CC)C.[I-].[Na+]>C(OCC)(=O)C>[C:1]([O:4][C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([O:9][CH2:15][C:16]([N:18]([CH2:21][CH3:22])[CH2:19][CH3:20])=[O:17])=[O:8])(=[O:3])[CH3:2]
Reactant: CC(=O)Oc1ccccc1C(=O)O
Reactant: CCN(CC)C(=O)CCl
Agent: [I-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CCN(CC)C(=O)COC(=O)c1ccccc1OC(C)=O
Yield: 70.5 %

Procedure:
To a mixture of acetylsalicylic acid (5.4 g. 0.03 mole) and 2-chloro-N,N-diethylacetamide (4.5 g, 0.03 mole) in 40 ml of ethyl acetate was added triethylamine (4.2 ml, 0.03 mole) and sodium iodide (0.45 g, 0.003 mole). The mixture was refluxed for 4 h. After cooling the mixture was filtered and the filtrate washed with 2M hydrochloric acid, 5% sodium bicarbonate and water. After drying over anhydrous sodium sulphate the solution was evaporated in vacuo leaving an oil which crystallized by trituration with ethanol. Recrystallization from 80% ethanol afforded 6.2 g (70%) of the title compound. Mp 75°-76° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:16]([CH3:33])[C:17](=[O:32])[CH2:18][N:19]2[C:24]3[CH:25]=[C:26]([Cl:30])[C:27]([Cl:29])=[CH:28][C:23]=3[O:22][CH2:21][C:20]2=[O:31])[CH2:9][N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[CH3:34][S:35]([NH:38][C:39]1[CH:44]=[CH:43][C:42](B(O)O)=[CH:41][CH:40]=1)(=[O:37])=[O:36]>>[Cl:30][C:26]1[C:27]([Cl:29])=[CH:28][C:23]2[O:22][CH2:21][C:20](=[O:31])[N:19]([CH2:18][C:17]([N:16]([CH3:33])[CH:8]([C:5]3[CH:6]=[CH:7][C:2]([C:42]4[CH:41]=[CH:40][C:39]([NH:38][S:35]([CH3:34])(=[O:36])=[O:37])=[CH:44][CH:43]=4)=[CH:3][CH:4]=3)[CH2:9][N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)=[O:32])[C:24]=2[CH:25]=1
Reactant: CN(C(=O)CN1C(=O)COc2cc(Cl)c(Cl)cc21)C(CN1CCOCC1)c1ccc(Br)cc1
Reactant: CS(=O)(=O)Nc1ccc(B(O)O)cc1
Product: CN(C(=O)CN1C(=O)COc2cc(Cl)c(Cl)cc21)C(CN1CCOCC1)c1ccc(-c2ccc(NS(C)(=O)=O)cc2)cc1

Procedure:
The title compound was prepared according to example 33, using the intermediate from step c) and {4-[(methylsulfonyl)amino]-phenyl}boronic acid, MS (ES) m/e 647 [M+H]+
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[F:19][C:20]1[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=1B(O)O.O>CC(C)=O>[F:19][C:20]1[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=1[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])=[CH:6][CH:7]=1
Reactant: CCCCCc1ccc(I)cc1
Reactant: OB(O)c1cccc(F)c1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: CCCCCc1ccc(-c2cccc(F)c2F)cc1
Temperature: 40 °C

Procedure:
1-Iodo-4-pentylbenzene (82 g, 0.3 mol), potassium carbonate (100 g, 0.72 mol), 2,3-difluorophenyl boronic acid (47 g, 0.3 mol), water (100 ml) and acetone (300 ml) were placed in a round-bottom three necked flask equipped with condenser, thermometer, mechanical stirrer, nitrogen inlet and outlet. The reaction flask was flushed with nitrogen and minor flow was held during whole reaction time. The mixture was heated up to the boiling point to degas the reaction system and then cooled down to 40° C. and the catalyst palladium acetate (0.1 g) was added. The temperature has increased by a few degrees and the solution turned brown. The mixture was refluxed for three days, then it was cooled down, poured on cold water and extracted with dichlorometane and the organic phase separated, dried over MgSO4 and dichlorometane was distilled off. The residue was distilled under reduced pressure at 0.2 mmHg collecting the fraction at 133° C. The colorless liquid fraction 41.5 g of was obtained, 53% of theor. yield.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:17]2[C:25]3[C:24]([NH2:26])=[N:23][CH:22]=[N:21][C:20]=3[NH:19][CH:18]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.[O:58]1CCO[CH:59]1[CH:63]1[CH2:68][CH2:67][CH2:66][CH:65](O)[CH2:64]1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1>[NH2:26][C:24]1[C:25]2[C:17]([C:4]3[CH:5]=[CH:6][C:7]([O:8][CH2:9][C:10]4[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=4)=[C:2]([Cl:1])[CH:3]=3)=[CH:18][N:19]([CH:65]3[CH2:66][CH2:67][CH2:68][CH:63]([CH:59]=[O:58])[CH2:64]3)[C:20]=2[N:21]=[CH:22][N:23]=1
Reactant: Nc1ncnc2[nH]cc(-c3ccc(OCc4cccc(F)c4)c(Cl)c3)c12
Reactant: OC1CCCC(C2OCCO2)C1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Nc1ncnc2c1c(-c1ccc(OCc3cccc(F)c3)c(Cl)c1)cn2C1CCCC(C=O)C1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
5-(3—CHloro-4-(3-fluorobenzyloxy)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine (prepared according to a similar procedure as described in Example 1) (1 equivalent) is placed in THF. Triphenyl phosphine (1.5 equivalents) is added, followed by dropwise addition of DEAD (3 equivalents). 3-(1,3-dioxolan-2-yl)cyclohexanol (1 equivalent) is added and the mixture is stirred at room temperature overnight. The reaction mixture is partitioned between EtOAc and water, the organic layer is separated, washed with water, brine, dried over Na2SO4 and filtered. The filtrate is concentrated under reduced pressure and suspended in acetone. p-Toluensulfonic acid (0.6 equivalent) is added and the mixture is refluxed for 4 h. The mixture is filtered, the filtrate is concentrated in vacuo and purified by column chromatography.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5](I)=[CH:4][N:3]=1.[N+:9]([C:12]1[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:13]=1[CH:14]=[O:15])([O-:11])=[O:10]>C1COCC1>[Cl:20][C:17]1[CH:18]=[CH:19][C:12]([N+:9]([O-:11])=[O:10])=[C:13]([CH:14]([C:5]2[CH:4]=[N:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[OH:15])[CH:16]=1
Reactant: O=Cc1cc(Cl)ccc1[N+](=O)[O-]
Reactant: Clc1ccc(I)cn1
Solvent: C1CCOC1
Product: O=[N+]([O-])c1ccc(Cl)cc1C(O)c1ccc(Cl)nc1
Temperature: -45 °C
Reaction time: 0.08 h

Procedure:
A solution of 1.0 g 2-chloro-5-iodopyridine (4.1 mmol, 1.0 eq.) in 10 mL anhyd. THF was stirred at −40° C. to −50° C. After five minutes, 2.2 mL of 2.1 MiPrMgBr/THF (4.6 mmol, 1.1 eq.) were added drop wise over 1 minute and the reaction mixture is maintained at −40 to −50° C. for 30 minutes. 1.3 g 2-nitro-5-chlorobenzaldehyde (7.0 mmol, 1.7 eq.) was then added and the reaction was maintained at −50° C. After 1 hour, the reaction was allowed to warm to −10° C., and quenched with 50 mL saturated brine after a further fifteen minutes. The crude product was extracted with EtOAc, dried on Na2SO4 and concentrated by rotary evaporation to yield desired product. MS: (M+H)/z=298.9
Reaction SMILES: C([O:3][CH:4](OCC)[CH2:5][O:6][C:7]1[C:14]([O:15][CH3:16])=[CH:13][CH:12]=[CH:11][C:8]=1[CH:9]=O)C>C(O)(=O)C>[CH3:16][O:15][C:14]1[C:7]2[O:6][C:5]([CH:4]=[O:3])=[CH:9][C:8]=2[CH:11]=[CH:12][CH:13]=1
Reactant: CCOC(COc1c(C=O)cccc1OC)OCC
Solvent: CC(=O)O
Product: COc1cccc2cc(C=O)oc12
Yield: 34.2 %

Procedure:
A stirred solution of 28 (2.0 g, 7.46 mmol) in acetic acid (10 mL) was refluxed for 24 h. After cooling, the solution was evaporated to dryness. The crude product was adsorbed on silica gel and purified by flash chromatography, eluting with hexane/EtOAc (4:1) to give 29 (450 mg, 34%) as a white solid. 1H NMR (500 MHz, CDCl3): δ: 9.89 (1H, s, CHO), 7.55 (1H, s, ArH), 7.30 (1H, d, J=6.95 Hz, ArH), 7.24 (1H, t, J=7.85, ArH), 6.97 (1H, d, J=6.90 Hz), 4.02 (3H, s, OCH3).
Reaction SMILES: [O:1]=[C:2]([NH:8][CH2:9][CH2:10][CH2:11][N:12]1[CH2:16][CH2:15][CH2:14][C:13]1=[O:17])[CH2:3][CH2:4][C:5]([OH:7])=O.[NH:18]1[CH2:24][CH2:23][CH2:22][C@H:19]1[CH2:20][OH:21].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C>[O:1]=[C:2]([NH:8][CH2:9][CH2:10][CH2:11][N:12]1[CH2:16][CH2:15][CH2:14][C:13]1=[O:17])[CH2:3][CH2:4][C:5]([N:18]1[CH2:24][CH2:23][CH2:22][C@H:19]1[CH2:20][OH:21])=[O:7]
Reactant: OC[C@@H]1CCCN1
Reactant: O=C(O)CCC(=O)NCCCN1CCCC1=O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: O=C(CCC(=O)N1CCC[C@H]1CO)NCCCN1CCCC1=O
Reaction time: 3 h
Yield: 55.2 %

Procedure:
To a solution of 4-oxo-4-[3-(2-oxo-1-pyrrolidinyl)propylamino]butyric acid (255 mg) and L-prolinol (118 mg) in DMF (5 ml) were added HOBt (157 mg) and DCC (249 mg) at -25° C. and the mixture was stirred at a temperature of -25°-0° C. for 3 hours. After 15 hours' stirring at room temperature, the precipitated dicyclohexylurea was filtered off, and the filtrate was concentrated. The residue was treated in the same manner as in Example 10-B) to give 189 mg of N-{4-oxo-4-[3-(2-oxo-1-pyrrolidinyl)propylamino]butanoyl}-L-prolinol.
Reaction SMILES: [O:1]=[C:2]1[NH:7][C:6](=[O:8])[CH:5]=[C:4]([CH2:9][CH2:10][CH3:11])[N:3]1[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:15][CH:14]=1.Br[CH2:28][C:29]([C:31]1[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=1)=[O:30].CN(C)C=O.[H-].[Na+]>C(OCC)(=O)C>[CH3:38][O:37][C:34]1[CH:35]=[CH:36][C:31]([C:29](=[O:30])[CH2:28][N:7]2[C:6](=[O:8])[CH:5]=[C:4]([CH2:9][CH2:10][CH3:11])[N:3]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]4[C:20]([C:25]#[N:26])=[CH:21][CH:22]=[CH:23][CH:24]=4)=[CH:15][CH:14]=3)[C:2]2=[O:1])=[CH:32][CH:33]=1
Reactant: COc1ccc(C(=O)CBr)cc1
Reactant: CCCc1cc(=O)[nH]c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCCc1cc(=O)n(CC(=O)c2ccc(OC)cc2)c(=O)n1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 88.2 %

Procedure:
To a mixture of 4′-[(2,4-dioxo-6-propyl-3,4-dihydropyrimidin-1(2H)-yl)methyl]biphenyl-2-carbonitrile (0.5 g), 2-bromo-1-(4-methoxyphenyl)ethanone (0.4 g) and N,N-dimethylformamide (10 mL) was added 60% sodium hydride (0.076 g), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with 5% potassium hydrogensulfate and then saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.63 g, 81%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:14]1[CH2:19][CH2:18][N:17]([S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[CH2:16][CH2:15]1.O1CCOCC1.C(=O)([O-])[O-].[K+].[K+].[CH3:37][N:38]([CH3:48])[C:39]1[CH:44]=[CH:43][C:42](B(O)O)=[CH:41][CH:40]=1>O>[CH3:37][N:38]([CH3:48])[C:39]1[CH:44]=[CH:43][C:42]([C:2]2[CH:3]=[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=2)[NH:7][CH:6]=[C:5]3[CH:14]2[CH2:15][CH2:16][N:17]([S:20]([CH2:23][CH3:24])(=[O:22])=[O:21])[CH2:18][CH2:19]2)=[CH:41][CH:40]=1
Reactant: CN(C)c1ccc(B(O)O)cc1
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(Br)cc23)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4ccc(N(C)C)cc4)cc23)CC1
Yield: 6.1 %

Procedure:
To a CEM microwave tube was added 5-bromo-3-[1-(ethylsulfonyl)-4-piperidinyl]-1H-indole-7-carboxamide (40 mg, 0.097 mmol), dioxane (2.8 mL) and a solution of potassium carbonate (40 mg, 0.289 mmol) in water (1.2 mL). To this mixture was added [4-(dimethylamino)phenyl]boronic acid (65 mg, 0.386 mmol) and chloro-2-(dimethylaminomethyl)-ferrocen-1-yl-(dinorbornylphosphine)palladium(II) (1 mg, 0.002 mmol). The vial was capped and the reaction was reacted in a CEM microwave for 10 min at 160° C. The reaction was concentrated under a stream of nitrogen at 80° C. The crude product was taken up in dimethyl sulfoxide (1 mL) and purified through a 1 g silica SPE cartridge eluting with dimethyl sulfoxide (4 mL). The dimethyl sulfoxide was concentrated in a Genevac at 65° C. for 3 h, and the residue was reconstituted in dimethyl sulfoxide (1 mL) and filtered through an acrodisc. The solution of crude product was then purified on the Agilent MDAP (UV 214 selection). The purified product was passed through a polymer-bound carbonate SPE cartridge to afford 2.7 mg of the title compound (6.2%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([CH3:19])[C:5]2[C:11](=[O:12])[N:10]([CH3:13])[C:9]3[CH:14]=[CH:15][CH:16]=[CH:17][C:8]=3[NH:7][C:6]=2[N:18]=1.[H-].[Na+].Br[CH2:23][CH2:24][CH2:25][Cl:26].C(Cl)Cl>CN(C)C=O>[Cl:26][CH2:25][CH2:24][CH2:23][N:7]1[C:8]2[CH:17]=[CH:16][CH:15]=[CH:14][C:9]=2[N:10]([CH3:13])[C:11](=[O:12])[C:5]2[C:4]([CH3:19])=[CH:3][C:2]([CH3:1])=[N:18][C:6]1=2
Reactant: Cc1cc(C)c2c(n1)Nc1ccccc1N(C)C2=O
Reactant: ClCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: Cc1cc(C)c2c(n1)N(CCCCl)c1ccccc1N(C)C2=O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2.47 gm of 6,11-dihydro-2,4,6-trimethyl-5H-pyrido-[2,3-b][1,5]benzodiazepin-5-one were dissolved in 15 ml of dimethyl formamide, 0.76 gm of 50% sodium hydride in mineral oil was added, and the mixture was stirred at room temperature for one hour. Then, 1.7 ml of 1-bromo-3-chloro-propane were added, and the mixture was stirred at room temperature for 5 hours. After standing overnight, 100 ml of methylene chloride were added and the reaction mixture was washed three times with water. The organic phase was dried over sodium sulfate and evaporated in vacuo at room temperature. The crystalline residue was digested with a mixture of 7 ml of chloroform and 7 ml of ethyl acetate, and the mixture was suction-filtered. The filter cake was recrystallized from absolute ethanol, yielding 52% of theory of 11-(3-chloro-propyl)-6,11-dihydro-2,4,6-trimethyl-5H-pyrido[2,3-b][1,5]benzodiazepin-5-one having a melting point of 161°-163° C.
Reaction SMILES: [NH:1]([C:3]1[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:6]=[C:5]([CH3:15])[N:4]=1)[NH2:2].[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([C:22](=O)[CH2:23][CH3:24])=[CH:18][CH:17]=1>C(O)C>[CH3:15][C:5]1[N:4]=[C:3]([NH:1][N:2]=[C:22]([C:19]2[CH:20]=[CH:21][C:16]([CH3:26])=[CH:17][CH:18]=2)[CH2:23][CH3:24])[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[N:6]=1
Reactant: Cc1nc(NN)cc(-c2ccccc2)n1
Reactant: CCC(=O)c1ccc(C)cc1
Solvent: CCO
Product: CCC(=NNc1cc(-c2ccccc2)nc(C)n1)c1ccc(C)cc1

Procedure:
The title compound was prepared from 4-hydrazino-2-methyl-6-phenylpyrimidine (300 mg, 1.5 mmol) and 1-p-Tolyl-propan-1-one (174 μL, 1.05 mmol) in 3.0 mL of ethanol by a procedure similar to example 1, step 4 yielding 110 mg (22%) of a white solid. HPLC Purity: 96%.
Reaction SMILES: [CH:1]1([CH2:6][N:7]([C:10]2[N:15]=[C:14]3[CH:16]=[CH:17][N:18]([CH3:19])[C:13]3=[CH:12][C:11]=2[C:20]#[N:21])[CH2:8][CH3:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Br:22]N1C(=O)CCC1=O.O>CN(C=O)C>[Br:22][C:16]1[C:14]2=[N:15][C:10]([N:7]([CH2:6][CH:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[CH2:8][CH3:9])=[C:11]([C:20]#[N:21])[CH:12]=[C:13]2[N:18]([CH3:19])[CH:17]=1
Reactant: CCN(CC1CCCC1)c1nc2ccn(C)c2cc1C#N
Reactant: O=C1CCC(=O)N1Br
Solvent: CN(C)C=O
Solvent: O
Product: CCN(CC1CCCC1)c1nc2c(Br)cn(C)c2cc1C#N
Reaction time: 0.5 h

Procedure:
To a mixture of 5-[N-(cyclopentylmethyl)-N-ethylamino]-1-methyl-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile (105 mg, 0.37 mmol) in DMF (2 mL) is added N-bromosuccinimide (NBS, 66 mg, 0.37 mmol) at 0° C. After stirring for 30 min, H2O is added, and the reaction mixture is extracted with EtOAc. The organic layer is dried over sodium sulfate, concentrated and purified by silica-gel column chromatography to give 3-bromo-5-[N-(cyclopentylmethyl)-N-ethylamino]-1-methyl-1H-pyrrolo[3,2-b]pyridine-6-carbonitrile as a yellow solid.
Reaction SMILES: Cl[C:2]1[C:11](Cl)=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:13])[CH:8]=2)[N:3]=1.CO[CH:16]([O:19]C)[CH2:17][NH2:18]>>[Cl:13][C:7]1[CH:8]=[C:9]2[C:4]([NH:3][C:16](=[O:19])[C:17]3[N:10]2[CH:11]=[CH:2][N:18]=3)=[CH:5][CH:6]=1
Reactant: COC(CN)OC
Reactant: Clc1ccc2nc(Cl)c(Cl)nc2c1
Product: O=c1[nH]c2ccc(Cl)cc2n2ccnc12

Procedure:
By reaction of 2,3,6-trichloroquinoxaline with aminoacetaldehyde dimethyl acetal, according to a procedure that is similar to that followed in example 1, there is obtained 8-chloroimidazo[1,2-a]quinoxaline-4(5H)-one (m.p. >300° C.). By reacting this product with 1-ethyl propylamine according to the method described in example 9, there is obtained 8-chloro-4-(1-ethylpropylamino)imidazo[1,2-a]quinoxaline. m.p. (DSC)=125.1° C.(onset); IR (KBr): 3406, 3105, 2964, 1532 cm-1 ; 1H-NMR (CDCl3 /CD3OD): δ8.4 (1H,s), 8.05 (1H,d, J=2 Hz), 7.8÷7.4 (3H,m), 3.85 (1H,m), 1.65 (4H,m), 0.95 (6H,t); UV (EtOH): λmax =230, 245, 289, 301, 326 nm. Elementary analysis for C15H17ClN4 (m.w. 288.78): calcd. C 62.39, H 5.93, N 19.40%; found C 62.17, H 6.02, N 19.46%.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH3:13])[N:11]=[CH:10][C:9]=2/[CH:14]=[CH:15]/[C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH2:25][S:26][CH3:27])=[CH:21][CH:20]=2)=[O:17])=[CH:4][CH:3]=1.ClC1C=CC=C(C(OO)=[O:36])C=1.S([O-])([O-])=O.[Na+].[Na+]>O1CCCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH3:13])[N:11]=[CH:10][C:9]=2/[CH:14]=[CH:15]/[C:16]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([CH2:25][S:26]([CH3:27])=[O:36])=[CH:23][CH:24]=2)=[O:17])=[CH:4][CH:3]=1
Reactant: CSCc1ccc(NC(=O)/C=C/c2cnn(C)c2-c2ccc(F)cc2)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cn1ncc(/C=C/C(=O)Nc2ccc(CS(C)=O)cc2)c1-c1ccc(F)cc1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 54.4 %

Procedure:
A mixture of (2E)-3-[5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl]-N-{4-[(methylthio)methyl]phenyl}acrylamide (600 mg), m-chloroperbenzoic acid (387 mg) and tetrahydrofuran (50 mL) was stirred at 0° C. for 20 min. A saturated aqueous sodium sulfite solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium hydrogen carbonate, and then with saturated brine, dried (MgSO4) and concentrated. The obtained solid was recrystallized from acetone-hexane to give (2E)-3-(5-(4-fluorophenyl)-1-methyl-1H-pyrazol-4-yl)-N-(4-((methylsulfinyl)methyl)phenyl)acrylamide (340 mg, yield 54%) as colorless prism crystals. melting point: 240-241° C.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][OH:9])[CH2:3][CH2:2]1.[N:10]([CH2:13][CH3:14])=[C:11]=[S:12]>C(Cl)Cl>[CH2:13]([NH:10][C:11]([N:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][OH:9])[CH2:3][CH2:2]1)=[S:12])[CH3:14]
Reactant: CCN=C=S
Reactant: OCCC1CCNCC1
Solvent: ClCCl
Product: CCNC(=S)N1CCC(CCO)CC1
Temperature: 25 °C
Reaction time: 10 h
Yield: 84 %

Procedure:
To a solution of 2-(piperidin-4-yl)ethanol (509 mg, 3.94 mmol) in CH2Cl2 (13 mL) was added isothiocyanatoethane (343 μL, 3.94 mmol). After stirring for 10 h at rt, the mixture was concentrated in vacuo to provide the titled compound (716 mg, 84%): 1H NMR (CDCl3) δ 5.38 (brs, 1H), 4.59 (d, J=13.6 Hz, 1H), 3.74-3.67 (m, 3H), 3.15 (d, J=12.8 Hz, 1H), 3.00 (t, J=13.2 Hz, 2H), 2.65 (t, J=12.4 Hz, 1H), 1.81-1.72 (m, 3H), 1.55-1.52 (m, 3H), 1.28-1.22 (m, 4H)
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]2[C:14]=1[CH2:13][C:12](=O)[CH2:11][CH2:10]2)(=[O:3])[CH3:2].[CH2:16]([NH2:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1C=CC=CC=1.CN(C=O)C.CC1C=CC(S(O)(=O)=O)=CC=1>[C:1]([NH:4][C:5]1[C:14]2[CH2:13][CH:12]([NH:23][CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:11][CH2:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)(=[O:3])[CH3:2]
Reactant: NCc1ccccc1
Reactant: CC(=O)Nc1cccc2c1CC(=O)CC2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CN(C)C=O
Solvent: c1ccccc1
Product: CC(=O)Nc1cccc2c1CC(NCc1ccccc1)CC2
Temperature: 25 °C
Reaction time: 18 h
Yield: 67 %

Procedure:
A solution of 8-acetamido-2-tetralone (15.5 g. 76 mmol), benzylamine (16.3 g, 150 mmol) and tosic acid (0.2 g) in benzene (200 mL) and DMF (50 mL) was refluxed with a Dean-Stark trap attached for 18 h. The solvent was evaporated and the residue dissolved in 1:1 methanol:THF (250 mL). After cooling in an ice bath, sodium cyanoborohydride was added and the mixture warmed to room temperature and stirred for 5 h. The mixture was basified with 12.5% NaOH and the solvent concentrated. The residue was dissolved in methylene chloride:water and filtered through a celite pad. The aqueous layer was extracted with methylene chloride, and the combined organic layers were dried over sodium sulfate, filtered and evaporated. The dark residue was purified by column chromatography (9:1 EtOAc:methanol) to give the product (15 g).
Reaction SMILES: C(OC1([CH2:23][C:24]2[CH:29]=[C:28]([O:30][CH3:31])[C:27]([O:32][CH3:33])=[C:26]([O:34][CH3:35])[CH:25]=2)C2C(=CC=C(C)C=2)N(CC)C1=O)(=O)C1C=CC=CC=1.[C:36]([O:44][CH:45]1[C:53]2[C:48](=[CH:49][CH:50]=[C:51]([CH3:54])[CH:52]=2)[N:47]([CH2:55][CH:56]([CH3:58])[CH3:57])[C:46]1=[O:59])(=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>>[C:36]([O:44][C:45]1([CH2:23][C:24]2[CH:25]=[C:26]([O:34][CH3:35])[C:27]([O:32][CH3:33])=[C:28]([O:30][CH3:31])[CH:29]=2)[C:53]2[C:48](=[CH:49][CH:50]=[C:51]([CH3:54])[CH:52]=2)[N:47]([CH2:55][CH:56]([CH3:57])[CH3:58])[C:46]1=[O:59])(=[O:43])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1
Reactant: Cc1ccc2c(c1)C(OC(=O)c1ccccc1)C(=O)N2CC(C)C
Reactant: CCN1C(=O)C(Cc2cc(OC)c(OC)c(OC)c2)(OC(=O)c2ccccc2)c2cc(C)ccc21
Product: COc1cc(CC2(OC(=O)c3ccccc3)C(=O)N(CC(C)C)c3ccc(C)cc32)cc(OC)c1OC

Procedure:
This compound was made in an analogous fashion to 1-ethyl-5-methyl-2-oxo-3-(3,4,5-trimethoxybenzyl)indolin-3-yl benzoate using 1-isobutyl-5-methyl-2-oxoindolin-3-yl benzoate.