Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1]/[N:2]=[C:3](\Cl)/[C:4]1[CH:15]=[CH:14][C:7]2[B:8]([OH:13])[O:9][C:10]([CH3:12])([CH3:11])[C:6]=2[CH:5]=1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]([C:26]([F:29])([F:28])[F:27])=[CH2:25])=[CH:20][C:19]=1[Cl:30].CC(=O)OCC>CN(C=O)C>[Cl:30][C:19]1[CH:20]=[C:21]([C:24]2([C:26]([F:29])([F:27])[F:28])[O:1][N:2]=[C:3]([C:4]3[CH:15]=[CH:14][C:7]4[B:8]([OH:13])[O:9][C:10]([CH3:12])([CH3:11])[C:6]=4[CH:5]=3)[CH2:25]2)[CH:22]=[CH:23][C:18]=1[Cl:17]
Reactant: C=C(c1ccc(Cl)c(Cl)c1)C(F)(F)F
Reactant: CC1(C)OB(O)c2ccc(/C(Cl)=N/O)cc21
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CC1(C)OB(O)c2ccc(C3=NOC(c4ccc(Cl)c(Cl)c4)(C(F)(F)F)C3)cc21
Temperature: 25 °C
Reaction time: 18 h
Yield: 24.4 %

Procedure:
To a solution of (Z)-N,1-dihydroxy-3,3-dimethyl-1,3-dihydrobenzo[c][1,2]oxaborole-5-carbimidoyl chloride (397 mg, 1.66 mmol) and 1,2-dichloro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (400 mg, 1.66 mmol) in DMF (5 mL) at rt was added TEA (168 mg, 1.66 mmol). The reaction mixture was stirred at rt for 18 h, poured into ice-water and extracted with EA (20 mL). The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography over silica gel eluted with PE:EA (6:1) to give the final title compound 5-(5-(3,4-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-3,3-dimethyl-benzo[c][1,2]oxaborol-1(3H)-ol (180 mg; yield 24.4%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 9.20 (s, 1H), 7.83-7.60 (m, 5H), 4.45 (d, J=18.8 Hz, 1H), 4.26 (d, J=18.4 Hz, 1H), 1.48 (s, 6H) ppm; HPLC purity: 96.8% at 220 nm and 97.5% at 254 nm; MS: m/z=444.3 (M+, ESI+).
Reaction SMILES: [C:1]([Cl:4])(Cl)=[O:2].[C:5]1([S:11]([C:14]2[CH:23]=[CH:22][C:17]3[NH:18][CH2:19][CH2:20][O:21][C:16]=3[CH:15]=2)(=[O:13])=[O:12])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.C(N(CC)CC)C>ClCCl>[C:5]1([S:11]([C:14]2[CH:23]=[CH:22][C:17]3[N:18]([C:1]([Cl:4])=[O:2])[CH2:19][CH2:20][O:21][C:16]=3[CH:15]=2)(=[O:13])=[O:12])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: O=S(=O)(c1ccccc1)c1ccc2c(c1)OCCN2
Reactant: O=C(Cl)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(Cl)N1CCOc2cc(S(=O)(=O)c3ccccc3)ccc21
Temperature: 25 °C

Procedure:
To a solution of phosgene (1.44 mL of a 1.8 M solution in dichloromethane, 2.64 mmol) at 0° C. was added a solution of 7-benzenesulfonyl-3,4-dihydro-2H-benzo[1,4]oxazine (0.663 g., 2.4 mmol) in 3 mL dichloromethane followed by dropwise addition of triethylamine (0.361 mL, 2.6 mmol) over three minutes. The reaction was allowed to warm to room temperature and was stirred for an hour. The reaction mixture was then concentrated in vacuo, and then dissolved in 50 mL dichloromethane which was removed in vacuo. A suspension of the crude residue in 60 mL of 1:1 ethyl ether: hexanes was washed with 3 times with 50 mL of 6N aqueous hydrogen chloride. The organic fractions were dried over MgSO4 and concentrated in vacuo to give 7-benzenesulfonyl-2,3-dihydro-benzo[1,4]oxazine-4-carbonyl chloride, which was used directly in the following step.
Reaction SMILES: [CH2:1]([C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11](B(O)O)=[CH:10][C:9]=2[CH:16]=1)[CH:2]([CH3:4])[CH3:3].Br[C:18]1[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][CH:19]=1.C(N(CC)CC)C>C(O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]2[O:12][C:11]([C:18]3[CH:25]=[CH:24][C:21]([CH:22]=[O:23])=[CH:20][CH:19]=3)=[CH:10][C:9]=2[CH:16]=1)[CH:2]([CH3:4])[CH3:3]
Reactant: CC(C)Cc1ccc2oc(B(O)O)cc2c1
Reactant: O=Cc1ccc(Br)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCO
Solvent: CCN(CC)CC
Product: CC(C)Cc1ccc2oc(-c3ccc(C=O)cc3)cc2c1
Yield: 64.2 %

Procedure:
A mixture of 5-isobutylbenzofuran-2-ylboronic acid (70 mg, 0.33 mmol), 4-bromobenzaldehyde (61 mg, 0.33 mmol), triethylamine (1.7 mL, 12.6 mmol) and bis(triphenylphosphine)palladium(II) chloride (12 mg, 0.017 mmol) in ethanol (10 mL) was irradiated in a microwave instrument at 100° C. for 20 min. The reaction mixture was cooled, and the solvent was removed. The residue was treated with water and extracted with ethyl acetate. The organic layer was dried and concentrated in vacuo (the aqueous work-up is optional). Purification by silica gel chromatography on ISCO system gave the title compound (59 mg, 65% yield): >99% purity by LCMS, ESI-MS: 279.2 (M+H)+.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][S:15][C:16]2[N:17]([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)[C:18]([C:21]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[C:26]([O:31][CH3:32])[CH:25]=3)([CH3:23])[CH3:22])=[CH:19][N:20]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:30][C:27]1[CH:28]=[CH:29][C:24]([C:21]([C:18]2[N:17]([C:33]3[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=3)[C:16]([S:15][CH2:14][CH:11]3[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]3)=[N:20][CH:19]=2)([CH3:23])[CH3:22])=[CH:25][C:26]=1[O:31][CH3:32]
Reactant: COc1cc(C(C)(C)c2cnc(SCC3CCN(C(=O)OC(C)(C)C)CC3)n2-c2ccc(F)cc2)ccc1Cl
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: COc1cc(C(C)(C)c2cnc(SCC3CCNCC3)n2-c2ccc(F)cc2)ccc1Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 79.1 %

Procedure:
To a 0° C. solution of tert-butyl-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)piperidine-1-carboxylate (0.755 g, 1.31 mmol) in DCM (4 mL) was added TFA (1 mL). After stirring at room temperature 2 h, when the reaction was determined to be complete by LCMS, the reaction was concentrated in vacuo. The residue was diluted with DCM, washed with satd NaHCO3 and brine, dried over MgSO4 and concentrated in vacuo to afford 4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)piperidine (0.491 g) as a white solid. MS (ES): 474 [M+H]+.
Reaction SMILES: C([O:5][C:6]([C:8]1[N:13]2[C:14](=[O:28])[CH:15]([NH:16][C:17](=[O:27])[CH2:18][S:19]([CH2:22][C:23]([F:26])([F:25])[F:24])(=[O:21])=[O:20])[C@H:12]2[S:11][CH2:10][C:9]=1[CH:29]([S:35][C:36]1[NH:40][N:39]=[N:38][N:37]=1)[CH2:30][CH2:31][C:32](=[O:34])[NH2:33])=[O:7])(C)(C)C.FC(F)(F)C(O)=O>C(#N)C>[F:25][C:23]([F:24])([F:26])[CH2:22][S:19]([CH2:18][C:17]([NH:16][CH:15]1[C:14](=[O:28])[N:13]2[C:8]([C:6]([OH:7])=[O:5])=[C:9]([CH:29]([S:35][C:36]3[NH:40][N:39]=[N:38][N:37]=3)[CH2:30][CH2:31][C:32](=[O:34])[NH2:33])[CH2:10][S:11][C@H:12]12)=[O:27])(=[O:20])=[O:21]
Reactant: CC(C)(C)OC(=O)C1=C(C(CCC(N)=O)Sc2nnn[nH]2)CS[C@@H]2C(NC(=O)CS(=O)(=O)CC(F)(F)F)C(=O)N12
Solvent: O=C(O)C(F)(F)F
Solvent: CC#N
Product: NC(=O)CCC(Sc1nnn[nH]1)C1=C(C(=O)O)N2C(=O)C(NC(=O)CS(=O)(=O)CC(F)(F)F)[C@H]2SC1
Reaction time: 3 h

Procedure:
The ester is dissolved in acetonitrile and trifluoroacetic acid is added. The solution is stirred for three hours, then evaporated to dryness to give the title compound.
Reaction SMILES: [CH2:1]([O:3][CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:15]=[CH:16][C:17]3[N:23]([S:24]([CH3:27])(=[O:26])=[O:25])[CH2:22][CH2:21][C:20]([C:28](O)=[O:29])=[CH:19][C:18]=3[CH:31]=2)=[CH:10][CH:9]=1)[CH3:2].S(Cl)(Cl)=O.[CH3:36][N:37]([CH:39]=O)[CH3:38]>C1COCC1>[CH2:1]([O:3][CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:15]=[CH:16][C:17]3[N:23]([S:24]([CH3:27])(=[O:25])=[O:26])[CH2:22][CH2:21][C:20]([C:28]([NH:23][C:17]4[CH:18]=[CH:31][C:14]([CH2:39][N:37]([CH3:36])[CH:38]5[CH2:5][CH2:4][O:3][CH2:1][CH2:2]5)=[CH:15][CH:16]=4)=[O:29])=[CH:19][C:18]=3[CH:31]=2)=[CH:10][CH:9]=1)[CH3:2]
Reactant: CCOCCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)O)CCN3S(C)(=O)=O)cc1
Reactant: CN(C)C=O
Solvent: O=S(Cl)Cl
Solvent: C1CCOC1
Product: CCOCCCOc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CN(C)C4CCOCC4)cc2)CCN3S(C)(=O)=O)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
In THF (5 ml) was dissolved 7-[4-(3-ethoxypropoxy)phenyl]-1-methanesulfonyl-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.20 g). To the solution were added, under ice-cooling, thionyl chloride (0.06 ml) and DMF (catalytic amount), and the mixture was stirred at room temperature for 2 hours. Under reduced pressure, the solvent was evaporated, and the residue was dissolved in THF (15 ml). The solution was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.11 g) and triethylamine (0.19 ml) in THF (5 ml), under ice-cooling, and the mixture was stirred under nitrogen atmosphere at room temperature overnight. Under reduced pressure, the solvent was evaporated. To the residue was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate, and the solvent was evaporated to give crude crystals, which were recrystallized from ethyl acetate/hexane to give 7-[4-(3-ethoxypropoxy)phenyl)-1-methanesulfonyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 8) (0.22 g) as colorless crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([C@@H:12]([CH3:17])[C:13]([F:16])([F:15])[F:14])[C:9]([OH:11])=O)=[CH:4][CH:3]=1.[NH2:18][C:19]1[C:20]([CH3:34])=[C:21]([CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH:22]=[CH:23][CH:24]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.N1C=CC=CC=1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([C@@H:12]([CH3:17])[C:13]([F:16])([F:15])[F:14])[C:9]([NH:18][C:19]2[C:20]([CH3:34])=[C:21]([CH2:25][CH2:26][C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28])[CH:22]=[CH:23][CH:24]=2)=[O:11])=[CH:6][CH:7]=1
Reactant: C[C@H]([C@H](C(=O)O)c1ccc(Cl)cc1)C(F)(F)F
Reactant: Cc1c(N)cccc1CCC(=O)OC(C)(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: Cc1c(CCC(=O)OC(C)(C)C)cccc1NC(=O)[C@H](c1ccc(Cl)cc1)[C@@H](C)C(F)(F)F
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 100 mg (0.38 mmol) of (2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoic acid, 88 mg (0.38 mmol) of tert-butyl 3-(3-amino-2-methylphenyl)propanoate, 213 mg (0.56 mmol) of 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and 1 ml of pyridine in 4 ml of DMF was stirred at room temperature overnight. After the reaction had ended, the reaction mixture was directly, without further work-up, separated into its components by preparative HPLC (mobile phase acetonitrile/water). This gave 151 mg (83% of theory) of the title compound as a colourless oil.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12]([C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][CH:22]=2)[NH:19][CH2:18][CH2:17]3)=[O:13])[CH:2]=1.C(N(CC)C(C)C)(C)C.[C:32](Cl)(=[O:34])[CH3:33]>ClCCCl>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([NH:11][C:12]([C:14]2[CH:15]=[C:16]3[C:20](=[CH:21][CH:22]=2)[N:19]([C:32](=[O:34])[CH3:33])[CH2:18][CH2:17]3)=[O:13])[CH:2]=1
Reactant: O=C(Nc1cnc2ccccc2c1)c1ccc2c(c1)CCN2
Reactant: CC(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCCl
Product: CC(=O)N1CCc2cc(C(=O)Nc3cnc4ccccc4c3)ccc21
Yield: 84 %

Procedure:
A solution of 2,3-dihydro-1H-indole-5-carboxylic acid quinolin-3-ylamide (77 mg, 0.266 mmol) and N,N-diisopropylethylamine (0.060 mL, 0.345 mmol) in 1,2-dichloroethane (2 mL) was treated with acetyl chloride (0.020 mL, 0.292 mmol). The resultant solution was stirred at room temperature overnight. The solvent was evaporated and the residue was triturated in water (1 mL) and saturated aqueous sodium bicarbonate (1 mL). The product was collected by filtration, to give the product 74 mg (84%). MS: m/z 332 (MH+). 1H NMR (DMSO-d6): δ 2.21 (s, 3H), 3.24 (t, 2 H), 4.18 (t, 2 H), 7.59 (t, 1 H), 7.67 (t, 1 H), 7.89-7.98 (m, 4 H), 8.15 (d, 1 H), 8.84 (s, 1 H), 9.14 (s, 1 H) and 10.566 (s, 1 H).
Reaction SMILES: [Br:1][C:2]1[S:3][C:4]2[C:10]([O:11][S:12]([C:15]([F:18])([F:17])[F:16])(=[O:14])=[O:13])=[C:9]([CH:19]([OH:25])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:8]([CH3:26])=[CH:7][C:5]=2[N:6]=1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.O.[O-]S(S([O-])=O)=O.[Na+].[Na+]>C(Cl)Cl>[Br:1][C:2]1[S:3][C:4]2[C:10]([O:11][S:12]([C:15]([F:18])([F:17])[F:16])(=[O:14])=[O:13])=[C:9]([C:19](=[O:25])[C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:8]([CH3:26])=[CH:7][C:5]=2[N:6]=1
Reactant: CCOC(=O)C(O)c1c(C)cc2nc(Br)sc2c1OS(=O)(=O)C(F)(F)F
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: CCOC(=O)C(=O)c1c(C)cc2nc(Br)sc2c1OS(=O)(=O)C(F)(F)F
Reaction time: 0.5 h
Yield: 84.8 %

Procedure:
To a solution of 29 (9.85 g, 20.6 mmol) in CH2Cl2 (100 mL) was added Dess-Martin periodinane (9.61 g, 22.6 mmol). After 30 min, water (75 mL) and saturated Na2S2O4 solution (75 mL) was added. The mixture was stirred vigorously for 30 min. The layers were separated, and the aqueous layer was extracted with CH2Cl2. The combined organic layers were dried, filtered, and concentrated in vacuo. The crude material was purified by column chromatography to give 8.32 g of 30. 1H-NMR: 400 MHz, (CDCl3) δ: 7.91 (s, 1H), 4.40 (q, 2H, J=7 Hz), 2.49 (s, 3H), 1.39 (t, 3H, J=7 Hz).
Reaction SMILES: [N+]([O-])([O-])=O.[CH3:5][C:6]1([CH3:45])[C:15]2[C:10](=[CH:11][C:12]([N+:16]([O-])=O)=[CH:13][CH:14]=2)[C:9](=[O:19])[N:8]([CH2:20][CH2:21][CH2:22][NH2+:23][CH2:24][CH2:25][CH2:26][N:27]2[C:36](=[O:37])[C:35]([CH3:39])([CH3:38])[C:34]3[C:29](=[CH:30][C:31]([N+:40]([O-])=O)=[CH:32][CH:33]=3)[C:28]2=[O:43])[C:7]1=[O:44].[ClH:46]>>[CH3:5][C:6]1([CH3:45])[C:15]2[C:10](=[CH:11][C:12]([NH2:16])=[CH:13][CH:14]=2)[C:9](=[O:19])[N:8]([CH2:20][CH2:21][CH2:22][NH:23][CH2:24][CH2:25][CH2:26][N:27]2[C:36](=[O:37])[C:35]([CH3:38])([CH3:39])[C:34]3[C:29](=[CH:30][C:31]([NH2:40])=[CH:32][CH:33]=3)[C:28]2=[O:43])[C:7]1=[O:44].[ClH:46]
Reactant: CC1(C)C(=O)N(CCC[NH2+]CCCN2C(=O)c3cc([N+](=O)[O-])ccc3C(C)(C)C2=O)C(=O)c2cc([N+](=O)[O-])ccc21
Agent: Cl
Agent: O=[N+]([O-])[O-]
Product: CC1(C)C(=O)N(CCCNCCCN2C(=O)c3cc(N)ccc3C(C)(C)C2=O)C(=O)c2cc(N)ccc21

Procedure:
N,N-Bis-[3-(3,4-dihydro-4,4-dimethyl-7-amino-1,3-dioxo-2(1H)-isoquinolyl)-propyl]-amine and its monohydrochloride was prepared analogous to Example 52 from N,N-bis-[3-(3,4-dihydro-4,4-dimethyl-7-nitro-1,3-dioxo-2(1H)-isoquinolyl)-propyl]-ammonium nitrate. M.p. of the monohydrochloride: above 300° C (sintering from 285° C); yield: 1 gm (41% of theory) (monohydrochloride).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([C:12](=[O:29])[C:13]3[CH:18]=[CH:17][C:16]([CH:19]([OH:28])[CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[CH3:27])=[CH:15][CH:14]=3)[CH2:10][CH2:9][CH2:8][CH:7]([CH2:30][C:31]([N:33]3[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]3)=[O:32])[C:6]=2[CH:40]=1.[C:41](OC(=O)C)(=[O:43])[CH3:42].S(=O)(=O)(O)O.C(=O)([O-])O.[Na+]>C(OCC)(=O)C.C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]([C:12](=[O:29])[C:13]3[CH:18]=[CH:17][C:16]([CH:19]([O:28][C:41](=[O:43])[CH3:42])[CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=4[CH3:27])=[CH:15][CH:14]=3)[CH2:10][CH2:9][CH2:8][CH:7]([CH2:30][C:31]([N:33]3[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]3)=[O:32])[C:6]=2[CH:40]=1
Reactant: CC(=O)OC(C)=O
Reactant: Cc1ccccc1CC(O)c1ccc(C(=O)N2CCCC(CC(=O)N3CCN(C)CC3)c3cc(Cl)ccc32)cc1
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: CC(=O)OC(Cc1ccccc1C)c1ccc(C(=O)N2CCCC(CC(=O)N3CCN(C)CC3)c3cc(Cl)ccc32)cc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a mixture of 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{4-[2-(2-methylphenyl)-1-hydroxyethyl]benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (0.5 g), acetic acid (5 ml) and acetic anhydride (3 ml) is added a drop of conc. sulfuric acid, and the mixture is stirred at room temperature for 12 hours, and subsequently stirred at a temperature from 60-70° C. for 6 hours. The reaction mixture is poured into ice-water, and thereto is added ethyl acetate (30 ml). The mixture is basified with sodium hydrogen carbonate, and extracted with ethyl acetate. The organic layer is washed successively with a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated. The residue is purified by silica gel column chromatography (solvent; methylene chloride:methanol=20:1) to give 7-chloro-5-[(4-methyl-1-piperazinyl)carbonylmethyl]-1-{4-[2-(2-methylphenyl)-1-acetyloxyethyl]-benzoyl}-2,3,4,5-tetrahydro-1H-benzazepine (0.36 g) as colorless amorphous.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:9])=[C:6]([CH:8]=1)[NH2:7].N1C=CC=CC=1.[C:16](Cl)(=[O:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]>ClC(Cl)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:9])=[C:6]([NH:7][C:16](=[O:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH:8]=1
Reactant: Nc1cc(Cl)ccc1O
Reactant: CCCCCCCCC(=O)Cl
Solvent: CC(Cl)Cl
Solvent: c1ccncc1
Product: CCCCCCCCC(=O)Nc1cc(Cl)ccc1O
Reaction time: 2 h

Procedure:
5-Chloro-2-hydroxy aniline, 10.3 g (0.072 mole), is dissolved in 200 ml dichloroethane, containing 25 ml pyridine. The solution is stirred at 70° C. while nonanoyl chloride is added slowly. The solution is stirred for 2 hours. Excess pyridine is removed by washing the product with 4N hydrochloric acid. The product is then passed through a florisil column and crystallized at -20°. There is obtained N-(5-chloro-2-hydroxyphenyl) nonanamide (M.P. 93.5-94.0). Analysis shows 4.94% nitrogen and 12.53% chlorine as against calculated values of 49.4% and 12.49% respectively, for C15H22ClNO2.
Reaction SMILES: [CH:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[N+:13]([O-:15])=[O:14])[C:6]([O:8][CH3:9])=[O:7])=O.[C:16](Br)(Br)([Br:18])[Br:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Br:17][C:16]([Br:18])=[CH:1][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[N+:13]([O-:15])=[O:14])[C:6]([O:8][CH3:9])=[O:7]
Reactant: BrC(Br)(Br)Br
Reactant: COC(=O)c1ccc([N+](=O)[O-])c(C=O)c1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COC(=O)c1ccc([N+](=O)[O-])c(C=C(Br)Br)c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of methyl 3-formyl-4-nitrobenzoate (23.7 mmol) and carbontetrabromide (8.66 g, 26.1 mmol) in dichloromethane (50 ml) was added dropwise a solution of triphenylphosphine (12.44 g, 47.5 mmol) in dichloromethane (50 ml) at 0° C. under a nitrogen atmosphere. The reaction was stirred for 1 h at 0° C. and then allowed to warm to room temperature. A small amount of white solid was formed. The solution was concentrated to 30 mL and then filtered. The organic solvent was concentrated under reduced pressure. The crude product was purified by flash column chromatography (SiO2, 10% EtOAc in hexanes as eluent) to afford methyl 3-(2,2-dibromovinyl)-4-nitrobenzoate was obtained as a light tan solid (32 g, 74%); 400 M Hz 1H NMR (CDCl3) 8.26 (br s, 1H), 8.12-8.18 (m, 2H), 7.75 (s, 1H), 3.98 (s, 3H).
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].[C:7](OC(=O)C)(=[O:9])[CH3:8]>>[C:7]([N:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6])(=[O:9])[CH3:8]
Reactant: O=C1CCCN1
Reactant: CC(=O)OC(C)=O
Product: CC(=O)N1CCCC1=O
Temperature: 25 °C
Yield: 96 %

Procedure:
A mixture of 112 g of 2-pyrrolidinone (9) and 249 mL of acetic anhydride was heated at reflux for 2 hours. The resultant mixture was allowed to cool to room temperature, was concentrated in vacuo, and was distilled (0.8 mm Hg, 68° C.) to provide 160 g of N-acetyl-2-pyrrolidinone (4) in 96% yield.
Reaction SMILES: F[C:2]1[CH:30]=[CH:29][CH:28]=[CH:27][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[NH:12][C:13](=[O:26])[CH2:14][NH:15][C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])=[O:5].[C:31]12(C(Cl)=O)[CH2:40]C3CC(CC(C3)[CH2:32]1)[CH2:38]2>>[C:3]12([C:4]([C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[NH:12][C:13](=[O:26])[CH2:14][NH:15][C:16]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])=[O:5])[CH2:40][CH:31]3[CH2:38][CH:28]([CH2:29][CH:30]([CH2:32]3)[CH2:2]1)[CH2:27]2
Reactant: O=C(Cl)C12CC3CC(CC(C3)C1)C2
Reactant: O=C(CNC(=O)OCc1ccccc1)Nc1ccccc1C(=O)c1ccccc1F
Product: O=C(CNC(=O)OCc1ccccc1)Nc1ccccc1C(=O)C12CC3CC(CC(C3)C1)C2
Yield: 6 %

Procedure:
According to the method used for the synthesis of the compound 28a, the titled compound (110 mg) is synthesized by using tert-butyl((2-trimethylstannylphenyl)-(2-(3-motolylureido)acethyl)amino)acetate (2.5 g) and adamantane-1-carbonylchloride (866 mg). Yield 6%.
Reaction SMILES: Cl[C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH:20]1(N(C)CC)[CH2:24][CH2:23][CH2:22][CH2:21]1>CN(C)C=O>[CH:20]1([CH2:4][N:3]([CH2:2][CH3:11])[C:2]2[C:11]([CH:12]=[O:13])=[CH:10][C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=2)[CH2:21][CH2:22][CH2:23][CH2:24]1
Reactant: CCN(C)C1CCCC1
Reactant: O=Cc1cc2ccccc2nc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCN(CC1CCCC1)c1nc2ccccc2cc1C=O
Temperature: 30 °C

Procedure:
2-Chloroquinoline-3-carbaldehyde (0.27 grams, 1.40 mmol) and potassium carbonate (0.579 grams, 1.4 mmol) were added to a 25 mL two-necked round bottomed flask. To this flask was added 3 mL of N,N-dimethylformamide (DMF), followed by the drop-wise addition of a dimethylformamide solution of cyclopentyl methyl ethyl amine (0.214 grams, 1.69 mmol). The resulting mixture was refluxed for 2 hours and then cooled to 25-35° C., after which the mixture was poured onto crushed ice (10 mL), and extracted with ethyl acetate (3×50 mL). The organic layer was washed with brine and dried over sodium sulfate. The solvent was evaporated in vacuo to provide the product as a yellow oil. Yield: 0.355 g (89%);
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:17]([N:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)=[N:16][C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:24]([O:26][CH3:27])=[O:25])[CH:14]=3)[N:9]=2)=[CH:4][CH:3]=1.CCN(CC)CC.[C:35](Cl)(=[O:37])[CH3:36]>ClCCl>[C:35]([N:21]1[CH2:22][CH2:23][N:18]([C:17]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[N:9][C:10]3[C:15]([N:16]=2)=[CH:14][C:13]([C:24]([O:26][CH3:27])=[O:25])=[CH:12][CH:11]=3)[CH2:19][CH2:20]1)(=[O:37])[CH3:36]
Reactant: COC(=O)c1ccc2nc(-c3ccc(F)cc3)c(N3CCNCC3)nc2c1
Reactant: CC(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1ccc2nc(-c3ccc(F)cc3)c(N3CCN(C(C)=O)CC3)nc2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 51.5 %

Procedure:
To a solution of methyl 2-(4-fluorophenyl)-3-(piperazin-1-yl)quinoxaline-6-carboxylate (180 mg, 0.49 mmol) in dichloromethane (10 ml) was added Et3N (59 mg, 0.59 mmol) and then acetyl chloride (39 mg, 0.59 mmol) was added dropwise. The resulting solution was stirred for 1 hour at room temperature and then quenched by the addition of ice-water (100 ml) and extracted with dichloromethane (3×15 ml). The organic layers were combined and dried over anhydrous magnesium sulfate and concentrated in vacuo to afford methyl 3-(4-acetylpiperazin-1-yl)-2-(4-fluorophenyl)quinoxaline-6-carboxylate as a yellow solid (103 mg, 51%).
Reaction SMILES: [C:1]([CH2:4][CH2:5][CH2:6][O:7][C:8]1[C:9]([Se:22][C:23]2[CH:33]=[CH:32][C:26]([C:27]([O:29]CC)=[O:28])=[CH:25][CH:24]=2)=[CH:10][C:11]2[C:12]([CH3:21])([CH3:20])[CH2:13][CH2:14][C:15]([CH3:19])([CH3:18])[C:16]=2[CH:17]=1)([OH:3])=[O:2].[OH-].[Na+]>C1COCC1.C(O)C>[C:1]([CH2:4][CH2:5][CH2:6][O:7][C:8]1[C:9]([Se:22][C:23]2[CH:24]=[CH:25][C:26]([C:27]([OH:29])=[O:28])=[CH:32][CH:33]=2)=[CH:10][C:11]2[C:12]([CH3:21])([CH3:20])[CH2:13][CH2:14][C:15]([CH3:19])([CH3:18])[C:16]=2[CH:17]=1)([OH:3])=[O:2]
Reactant: CCOC(=O)c1ccc([Se]c2cc3c(cc2OCCCC(=O)O)C(C)(C)CCC3(C)C)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: C1CCOC1
Product: CC1(C)CCC(C)(C)c2cc([Se]c3ccc(C(=O)O)cc3)c(OCCCC(=O)O)cc21

Procedure:
In manner similar to that of Example 2, by reaction of 250 mg (0.46 mmol) of ethyl 4-[3-(3-carboxypropoxy)-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthylselanyl]benzoate with 183 mg (4.6 mmol) of sodium hydroxide in a THF/ethanol mixture (5 ml/5 ml), 172 mg (76%) of a white powder are obtained. m.p.: 230° C.