Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([CH:11]=[CH:12][C:13](O)=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.O1CCCC1.B.O.Cl>CO.O1CCCC1.[C].[Pd]>[C:1]1([CH2:11][CH2:12][CH2:13][OH:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=C(O)C=Cc1cccc2ccccc12
Agent: [Pd]
Agent: B
Agent: Cl
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: OCCCc1cccc2ccccc12
Temperature: 25 °C
Reaction time: 13 h
Yield: 100 %

Procedure:
3-(1-Naphthyl) acrylic acid (5.00 g) was dissolved in methanol (30 ml) and tetrahydrofuran (50 ml), 10% palladium carbon (2.40 g) was added, and the mixture was stirred under a hydrogen atmosphere at room temperature for 13 hr. The reaction container was purged with nitrogen, the solution was filtered, and the filtrate was concentrated to give a white solid (5.00 g. The white solid was dissolved in tetrahydrofuran (100 ml), and a tetrahydrofuran-borane.tetrahydrofuran solution (1 mol/l, 27.4 ml) was added dropwise to the mixture under ice-cooling, and the mixture was stirred under ice-cooling for 1 hr, and further at room temperature for 18 hr. To the reaction mixture was added water, and 1M aqueous hydrochloric acid solution was added. The mixture was extracted with ethyl acetate, washed with water, saturated aqueous sodium hydrogen carbonate solution and 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 object product (4.70 g) as a colorless oil.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:25])=[C:8]2[C:14]([Br:15])=[C:13]([Br:16])[N:12]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:9]2=[CH:10][N:11]=1)=[O:5])[CH3:2].C1C(=O)N([Br:33])C(=O)C1.C(OOC(C1C=CC=CC=1)=O)(C1C=CC=CC=1)=O>>[CH2:1]([O:3][C:4]([C:6]1[C:7]([OH:25])=[C:8]2[C:14]([Br:15])=[C:13]([Br:16])[N:12]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[C:9]2=[C:10]([Br:33])[N:11]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1ncc2c(c1O)c(Br)c(Br)n2Cc1ccc(F)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Product: CCOC(=O)c1nc(Br)c2c(c1O)c(Br)c(Br)n2Cc1ccc(F)cc1

Procedure:
Prepared in analogy to that of Example 103(a) from 2,3-dibromo-1-(4-fluoro-benzyl)-4-hydroxy-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid ethyl ester, NBS and BzOOBz. The title compound, ESI MS (m/z): 549 (M+H)+.
Reaction SMILES: C(O[C:6]([N:8](C)[CH2:9][C:10]([O:12][CH2:13][N:14]1[C:18]2=[N:19][CH:20]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[CH:22]=[C:17]2[C:16]([C:30](=[O:46])[C:31]2[C:36]([F:37])=[CH:35][CH:34]=[C:33]([NH:38][S:39]([CH2:42][CH2:43][CH3:44])(=[O:41])=[O:40])[C:32]=2[F:45])=[CH:15]1)=[O:11])=O)(C)(C)C.Cl>CCOC(C)=O>[ClH:29].[CH3:6][NH:8][CH2:9][C:10]([O:12][CH2:13][N:14]1[C:18]2=[N:19][CH:20]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[CH:22]=[C:17]2[C:16]([C:30](=[O:46])[C:31]2[C:36]([F:37])=[CH:35][CH:34]=[C:33]([NH:38][S:39]([CH2:42][CH2:43][CH3:44])(=[O:40])=[O:41])[C:32]=2[F:45])=[CH:15]1)=[O:11]
Reactant: CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2cn(COC(=O)CN(C)C(=O)OC(C)(C)C)c3ncc(-c4ccc(Cl)cc4)cc23)c1F
Agent: Cl
Solvent: CCOC(C)=O
Product: CCCS(=O)(=O)Nc1ccc(F)c(C(=O)c2cn(COC(=O)CNC)c3ncc(-c4ccc(Cl)cc4)cc23)c1F
Yield: 111.6 %

Procedure:
A mixture of (5-(4-chlorophenyl)-3-(2,6-difluoro-3-(propylsulfonamido)benzoyl)-1H-pyrrolo[2,3-b]pyridin-1-yl)methyl 2-((tert-butoxycarbonyl)(methyl)amino)acetate (0.33 g, 0.48 mmol) and a saturated solution of HCl in EtOAc (3 mL) was stirred at rt for 3 h. The mixture was filtered to afford the title compound as a white solid (168 mg, 56%). The title compound was characterized by LCMS and 1H NMR as shown below:
Reaction SMILES: [CH2:1]([N:3]([CH2:9][CH3:10])[C:4](=[O:8])[CH2:5][NH:6][CH3:7])[CH3:2].[C:11]([NH:14][C:15]1[S:16][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:18][N:19]=1)(=[O:13])[CH3:12].CCN(C(C)C)C(C)C>C(Cl)Cl>[C:11]([NH:14][C:15]1[S:16][C:17]([S:20]([N:6]([CH3:7])[CH2:5][C:4]([N:3]([CH2:9][CH3:10])[CH2:1][CH3:2])=[O:8])(=[O:21])=[O:22])=[CH:18][N:19]=1)(=[O:13])[CH3:12]
Reactant: CCN(CC)C(=O)CNC
Reactant: CC(=O)Nc1ncc(S(=O)(=O)Cl)s1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCN(CC)C(=O)CN(C)S(=O)(=O)c1cnc(NC(C)=O)s1
Temperature: 25 °C
Yield: 59 %

Procedure:
A mixture of N,N-diethyl-2-methylamino-acetamide (12 mmol), 2-acetylamino-thiazole-5-sulfonyl chloride (12 mmol) (prepared as described in J. Am. Chem. Soc 69, 2063, 1947), DIPEA (15 mmol) in DCM (50 mL) was stirred at room temperature over night. The reaction mixture was diluted with DCM (50 mL) washed with 10% aq NaHSO4, water and brine, dried and concentrated to give 2-[(2-acetylamino-thiazole-5-sulfonyl)-methyl-amino]-N,N-diethylacetamide (59%) as pale yellow crystals. This was suspended in EtOH (10 mL) and added 8N HCl in dioxane (10 mL) and heated for 3H at 80° C. and then cooled to room temperature and concentrated in vacuo to give 2-[(2-amino-thiazole-5-sulfonyl)-methyl-amino]-N,N-diethyl-acetamide as a hydrochloride as colourless crystals.
Reaction SMILES: [CH2:1]([N:5]1[C:9]([CH2:10]O)=[C:8]([F:12])[N:7]=[C:6]1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:2][CH2:3][CH3:4].S(Cl)(Cl)=O.[CH2:23]([NH2:33])[C:24]1[CH:32]=[CH:31][C:30]2[O:29][CH2:28][O:27][C:26]=2[CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>ClCCl.CN(C=O)C.C(OCC)(=O)C>[O:29]1[C:30]2[CH:31]=[CH:32][C:24]([CH2:23][NH:33][CH2:10][C:9]3[N:5]([CH2:1][CH2:2][CH2:3][CH3:4])[C:6]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)=[N:7][C:8]=3[F:12])=[CH:25][C:26]=2[O:27][CH2:28]1
Reactant: CCCCn1c(-c2ccccc2)nc(F)c1CO
Reactant: NCc1ccc2c(c1)OCO2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=S(Cl)Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCCCn1c(-c2ccccc2)nc(F)c1CNCc1ccc2c(c1)OCO2
Temperature: 0 °C
Reaction time: 2 h

Procedure:
Compound 143 (76 mg, 0.30 mmol) is dissolved in 2 ml dichloromethane and cooled to 0° C. Thionyl chloride (0.05 mL) is added and the resulting solution is stirred at room temperature for 2 h. The solvent and excess thionyl chloride are evaporated. The residue is dissolved in 1.0 ml DMF and added to a solution of piperonyl amine (227 mg, 1.5 mmol) in DMF (2 mL) containing 100 mg potassium carbonate. The resulting mixture is stirred at room temperature for 2 h, then diluted with 20 ml of ethyl acetate, washed with water and brine, dried, and concentrated. The resulting residue is purified with silica gel chromatography (hexanes/ethyl acetate, from 2:1 to 1:1) to provide compound 144. MS (+VE) m/z 382 (M+1).
Reaction SMILES: [Br:1][C:2]1[CH:23]=[C:22]([O:24][CH3:25])[C:5]2[N:6]([CH2:18][CH2:19][O:20][CH3:21])[C:7]([C:9]3[CH:14]=[CH:13][C:12]([CH:15]([CH3:17])[CH3:16])=[CH:11][CH:10]=3)=[N:8][C:4]=2[CH:3]=1.[Br:26]Br.CCOC(C)=O>C(O)(=O)C>[Br:26][C:3]1[C:4]2[N:8]=[C:7]([C:9]3[CH:14]=[CH:13][C:12]([CH:15]([CH3:17])[CH3:16])=[CH:11][CH:10]=3)[N:6]([CH2:18][CH2:19][O:20][CH3:21])[C:5]=2[C:22]([O:24][CH3:25])=[CH:23][C:2]=1[Br:1]
Reactant: COCCn1c(-c2ccc(C(C)C)cc2)nc2cc(Br)cc(OC)c21
Reactant: BrBr
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: COCCn1c(-c2ccc(C(C)C)cc2)nc2c(Br)c(Br)cc(OC)c21
Temperature: 25 °C
Reaction time: 3 h
Yield: 6.2 %

Procedure:
To a solution of 403 mg (1.0 mmol) 5-bromo-2-(4-isopropyl-phenyl)-7-methoxy-1-(2-methoxy-ethyl)-1H-benzoimidazole in 8 ml glacial acetic acid, 240 mg (1.5 mmol) bromine is slowly added at 10° C. The reaction mixture is allowed to warm to room temperature and is stirred for 3 h. 250 ml EtOAc are added and this solution is washed 1 n NaOH (2×), water and brine, dried over MgSO4, filtered and concentrated in vacuo. The residue is recrystallized from EtOAc/hexane to afford 30 mg of the title compound as colorless crystals.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:4]=[C:5]([CH:20]=[CH:21][CH:22]=1)[O:6][CH2:7][C:8]1[N:9]=[C:10]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[O:11][C:12]=1[CH3:13].[CH2:23]([N:30]1[CH:34]=[C:33]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[C:32]([OH:40])=[N:31]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH2:23]([N:30]1[CH:34]=[C:33]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[C:32]([O:40][CH2:2][C:3]2[CH:22]=[CH:21][CH:20]=[C:5]([O:6][CH2:7][C:8]3[N:9]=[C:10]([C:14]4[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=4)[O:11][C:12]=3[CH3:13])[CH:4]=2)=[N:31]1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: CCOC(=O)c1cn(Cc2ccccc2)nc1O
Reactant: Cc1oc(-c2ccccc2)nc1COc1cccc(CCl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1cn(Cc2ccccc2)nc1OCc1cccc(OCc2nc(-c3ccccc3)oc2C)c1
Temperature: 80 °C
Reaction time: 15 h
Yield: 87.2 %

Procedure:
A mixture of 4-(3-chloromethylphenoxy)methyl-5-methyl-2-phenyl-1,3-oxazole (2.10 g), ethyl 1-benzyl-3-hydroxy-1H-pyrazole-4-carboxylate (1.50 g), potassium carbonate (0.84 g) and N,N-dimethylformamide (50 mL) was stirred at 80° C. for 15 hrs. Water was poured into the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (1:2, v/v) to give ethyl 1-benzyl-3-({3-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]benzyl}oxy)-1H-pyrazole-4-carboxylate as colorless crystals (2.78 g, yield 87%). Recrystallization from ethyl acetate-hexane gave colorless prism crystals. melting point: 95-96° C.
Reaction SMILES: [H-].[Na+].[F:3][C:4]([F:39])([F:38])[C:5]1[CH:6]=[C:7]([CH2:15][NH:16][C:17](=[O:37])[CH2:18][C:19]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:24]=2)=[O:20])[CH:8]=[CH:9][C:10]=1[C:11]([F:14])([F:13])[F:12].C(OOC(=O)C1C=CC=CC=1)(=[O:47])C1C=CC=CC=1>CN(C)C=O>[F:3][C:4]([F:38])([F:39])[C:5]1[CH:6]=[C:7]([CH2:15][NH:16][C:17](=[O:37])[CH:18]([C:19]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[C:25]([C:33]([F:34])([F:36])[F:35])[CH:24]=2)=[O:20])[OH:47])[CH:8]=[CH:9][C:10]=1[C:11]([F:14])([F:13])[F:12]
Reactant: O=C(OOC(=O)c1ccccc1)c1ccccc1
Reactant: O=C(CC(=O)NCc1ccc(C(F)(F)F)c(C(F)(F)F)c1)NCc1ccc(C(F)(F)F)c(C(F)(F)F)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C(NCc1ccc(C(F)(F)F)c(C(F)(F)F)c1)C(O)C(=O)NCc1ccc(C(F)(F)F)c(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a stirred suspension of 0.515 g of sodium hydride (57% in mineral oil) in 10 ml of dry dimethylformamide, under a nitrogen atmosphere, add dropwise a solution of 6.0 g N,N'-bis-[3,4-bis-(trifluoromethyl)phenyl]methylmalonamide dissolved in 35 ml of dry dimethylformamide. Upon cessation of gas evolution, cool the resulting orange solution to about 0°-5° C. and add dropwise a solution of 2.8 g dibenzoyl peroxide in 30 ml of dry dimethylformamide. Stir the resulting white suspension for 16 hours at room temperature under a nitrogen atmosphere, quench with aqueous sodium bisulfite and extract with ether. Wash the ether extract with water, dry over sodium sulfate and remove the ether in vacuo. Chromatograph the residue on 200 g of acidic alumina and elute with hexane/methylene chloride (3:2) to separate the product from unreacted starting material. Recrystallize this material from 1:2 benzene/hexane to give the title compound [Rf =0.55 (tlc-silica gel, 7:1 chloroform/hexane].
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C@@H:12]([NH:17][C:18](=[O:42])[CH2:19][NH:20][C:21](=[O:41])[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([NH:28][C:29]3[N:30](C(OC(C)(C)C)=O)[CH2:31][CH2:32][N:33]=3)[CH:23]=2)[CH2:13][C:14]([OH:16])=[O:15])[CH:5]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:7]=1>C(O)(C(F)(F)F)=O.C(#N)C>[Br:1][C:2]1[CH:3]=[C:4]([C@@H:12]([NH:17][C:18](=[O:42])[CH2:19][NH:20][C:21](=[O:41])[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([NH:28][C:29]3[NH:33][CH2:32][CH2:31][N:30]=3)[CH:23]=2)[CH2:13][C:14]([OH:16])=[O:15])[CH:5]=[C:6]([C:8]([CH3:9])([CH3:11])[CH3:10])[CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CCN=C1Nc1cccc(C(=O)NCC(=O)N[C@@H](CC(=O)O)c2cc(Br)cc(C(C)(C)C)c2)c1
Solvent: O=C(O)C(F)(F)F
Solvent: CC#N
Product: CC(C)(C)c1cc(Br)cc([C@H](CC(=O)O)NC(=O)CNC(=O)c2cccc(NC3=NCCN3)c2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The crude (S)-3-(3-bromo-5-(tert-butyl)phenyl)-3-(2-(3-((1-(tert-butoxycarbonyl)-4,5-dihydro-1H-imidazol-2-yl)amino)benzamido)acetamido)propanoic acid from Step #2 was dissolved in 20% TFA in acetonitrile (10 mL) and the reaction mixture was stirred at room temperature overnight to give a colorless solution. The solvent was evaporated in vacuo to give a colorless viscous residue. The crude product was purified by reverse-phase HPLC with a gradient 10-70% CH3CN in water containing 0.05% TFA to give the desired product (Example 7), after lyophilization, as a colorless lyophilized solid (364 mg). LC/MS analysis of the product shows the desired product's mass: m/z 544 (79BrM+H), and m/z 546 (81BrM+H); Calcd for C25H30BrN5O4: 544.44. 1H NMR (400 MHz, DMSO-d6): δ 1.27 (s, 9H, (CH3)3C—), 2.71 (d, J=7.30 Hz, 2H, —CH2—COOH), 3.68 (brs, 3H), 3.92 (d, J=5.80 Hz, 2H), 5.20 (q, J=7.5 Hz, 1H, —NH—CH—CH2—COOH), 7.36 (brd, J=9.8 Hz, 2H), 7.41 (brd/m, 2H), 7.55 (t, J=7.8 Hz, 1H), 7.73 (brs, 1H), 7.79 (d, J=7.8 Hz, 1H), 8.46 (s, 2H), 1H), 8.55 (d, J=7.30 Hz, 1H), 8.80 (appt, J=5.80 Hz, 1H), 10.62 (s, 1H), 12.37 (brs, 1H, —COOH). 1H NMR spectrum of the sample was consistent with the suggested structure of the product.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:23])[CH2:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:24]Br>C(O)(=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:23])[CH:16]([Br:24])[C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: BrBr
Reactant: O=C(Cc1ccncc1)c1ccc(OCc2ccccc2)cc1
Solvent: CC(=O)O
Product: O=C(c1ccc(OCc2ccccc2)cc1)C(Br)c1ccncc1
Reaction time: 2 h
Yield: 95.4 %

Procedure:
To a solution of 1-(4-(benzyloxy)phenyl)-2-(pyridin-4-yl)ethanone (1.39 g, 4.58 mmol) in acetic acid was added a solution of bromine (0.72 g, 4.58 mmol) in acetic acid (3 mL). After stirring 2 h, the solid was collected via filtration and washed with acetic acid to provide 1.67 g (96%) of the title compound as a pale yellow solid. 1H NMR (400 MHz, DMSO) δ: 5.21 (s, 1H), 7.15 (d, 2H), 7.42 (m, 3H), 7.87 (m, 1H), 8.06 (d, 2H), 8.77 (m, 1H). MS m/z: 382 [M+1]+.
Reaction SMILES: [O:1]([C:8]1[CH:15]=[CH:14][C:11]([CH:12]=O)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[CH2:17]([S:19][CH2:20][CH2:21][NH2:22])[CH3:18]>>[CH2:17]([S:19][CH2:20][CH2:21][NH:22][CH2:12][C:11]1[CH:14]=[CH:15][C:8]([O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:9][CH:10]=1)[CH3:18]
Reactant: O=Cc1ccc(Oc2ccccc2)cc1
Reactant: CCSCCN
Agent: Cl
Product: CCSCCNCc1ccc(Oc2ccccc2)cc1
Yield: 94.6 %

Procedure:
Following the procedure described in Example 68A, 4-phenoxybenzaldehyde (1.98 g, 10 mmol) and 2-(ethylthio)ethylamine hydrogen chloride (1.42 g, 10 mmol) were combined to give the title compound (2.72 g, 95%). 1H NMR (300 MHz, CDCl3), δ 7.33 (m, 4 H), 7.09 (t, 1 H), 6.98 (m, 4 H), 3.78 (s, 2 H), 2.84 (t, 2 H), 2.71 (t, 2 H), 2.54 (q, 2 H), 1.26 (t, 3 H).
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([NH:9][C:10](=[S:18])OC2C=CC=CC=2)=[C:4]([O:19][CH3:20])[CH:3]=1.[CH3:21][O:22][C:23]1[CH:24]=[C:25]([N:31]2[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]2)[CH:26]=[C:27]([O:29][CH3:30])[CH:28]=1.C1CCN2C(=NCCC2)CC1>O1CCCC1>[CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([NH:9][C:10]([N:34]2[CH2:33][CH2:32][N:31]([C:25]3[CH:24]=[C:23]([O:22][CH3:21])[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=3)[CH2:36][CH2:35]2)=[S:18])=[C:4]([O:19][CH3:20])[CH:3]=1
Reactant: COc1cc(OC)cc(N2CCNCC2)c1
Reactant: COc1cc(C)c(C)cc1NC(=S)Oc1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Solvent: C1CCOC1
Product: COc1cc(OC)cc(N2CCN(C(=S)Nc3cc(C)c(C)cc3OC)CC2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 84 %

Procedure:
Phenyl N-(4,5-dimethyl-2-methoxyphenyl)thiocarbamate(0.2 g, 0.7 mmol) and 1-(3,5-dimethoxyphenyl)piperazine(0.16 g, 0.7 mmol) were dissolved in tetrahydrofuran(10 ml) and thereto DBU(0.11 g, 0.7 mmole) was added, followed by stirring at room temperature for 2 hours. The resulting product was concentrated and purified by chromatography to obtain the titled compound.
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:10]=[C:11]([N:15]3[CH2:20][CH2:19][C:18](=[O:21])[CH2:17][CH2:16]3)[CH:12]=[CH:13][CH:14]=2)O1.[Cl:23][C:24]1[N:29]=[C:28](Cl)[CH:27]=[CH:26][N:25]=1>>[Cl:23][C:24]1[N:29]=[C:28]([C:9]2[CH:10]=[C:11]([N:15]3[CH2:16][CH2:17][C:18](=[O:21])[CH2:19][CH2:20]3)[CH:12]=[CH:13][CH:14]=2)[CH:27]=[CH:26][N:25]=1
Reactant: Clc1ccnc(Cl)n1
Reactant: CC1(C)OB(c2cccc(N3CCC(=O)CC3)c2)OC1(C)C
Product: O=C1CCN(c2cccc(-c3ccnc(Cl)n3)c2)CC1

Procedure:
1-(3-(2-Chloropyrimidin-4-yl)phenyl)piperidin-4-one was prepared from 1-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)piperidin-4-one and 2,4-dichloropyrimidine according to procedure B.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:27])[C@H:4]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=1)[NH:5][C:6]([C:8]1([CH2:13][CH2:14][O:15][CH3:16])[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7].[CH3:28]I>CN(C=O)C.[Ag]=O>[CH3:1][O:2][C:3](=[O:27])[C@H:4]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][CH:19]=1)[N:5]([C:6]([C:8]1([CH2:13][CH2:14][O:15][CH3:16])[CH2:12][CH2:11][CH2:10][CH2:9]1)=[O:7])[CH3:28]
Reactant: CI
Reactant: COCCC1(C(=O)N[C@@H](Cc2ccc([N+](=O)[O-])cc2)C(=O)OC)CCCC1
Agent: O=[Ag]
Solvent: CN(C)C=O
Product: COCCC1(C(=O)N(C)[C@@H](Cc2ccc([N+](=O)[O-])cc2)C(=O)OC)CCCC1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To a suspension of N-[[1-(2-methoxyethyl)cyclopentyl]carbonyl]-4-nitro-L-phenylalanine methyl ester (2.73 mmol, 1.03 g) and silver oxide (10.9 mmol, 2.53 g) in DMF (25 mL) was added methyl iodide (160 mmol, 10 mL) at room temperature. The suspension was stirred for 2 days at room temperature at which time TLC analysis of the mixture indicated the presence of starting material. An additional 10 mL (160 mmol) of methyl iodide and 2 g (8.6 mmol) of silver oxide were added, respectively. The suspension was stirred for 24 h and the solid was filtered through a pad of celite and was washed with ethyl acetate (30 mL) and methanol (30 mL). The filtrate was concentrated and the residue was extracted with ethyl acetate (3×30 mL).The organic layer was washed with water (20 mL) and brine solution (20 mL) and was dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent gave a crude compound which was purified by silica gel column chromatography to obtain 530 mg (50%) as a light brown oil. HR MS (C20H28N2O6): Obs. mass, 392.1940. Calcd. mass, 392.1947 (M+).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([SH:8])[CH:5]=[CH:6][CH:7]=1.[CH:9]1(Br)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH:9]1([S:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1
Reactant: Sc1cccc(Br)c1
Reactant: BrC1CCCCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Brc1cccc(SC2CCCCC2)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 54.3 %

Procedure:
To a stirred solution of 3-bromobenzenethiol (5.00 g) in DMF (100 ml) was added cyclohexyl bromide (4.31 g) and potassium carbonate (7.31 g). The mixture was stirred at room temperature under nitrogen for 18 h. The reaction mixture was partitioned between 2N HCl and EtOAC. The organic phase was washed with brine and dried (MgSO4). Filtration and removal of the solvent under reduced pressure gave the title compound (3.89 g). Tlc (silica) (4:1 cyclohexane-diethyl ether) Rf=0.90.