Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[N:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCN([CH2:32][CH3:33])CC>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([N:24]1[CH2:23][CH2:22][N:21]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[O:14][CH:11]2[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:13][CH2:12]2)[CH2:26][CH2:25]1)([O:3][CH2:4][C:33]1[CH:32]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:2]
Reactant: CCN(CC)CC
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2ccccc2N2CCNCC2)CC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccccc2N2CCN(C(=O)OCc3ccccc3)CC2)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 71.4 %

Procedure:
To a solution of 4-[2-(N-boc-piperidin-4-yloxy)-phenyl]-piperazine (1.5 g, 4.1 mol, 1.0 eq.) in DCM (20 mL) was added Et3N (0.8 mL, 5.74 mmol, 1.4 eq.), di-carbobenzoyloxy anhydride (1.4 g, 4.9 mmol, 1.2 eq.) and DMAP (25 mg, 0.2 mmol, 0.5 eq.). The mixture was stirred at r.t. overnight. The solution was diluted with DCM (100 mL) and washed with saturated aqueous NaHCO3 (50 mL) and brine (50 mL). The organic layer was dried (Na2SO4), filtered and concentrated to afford the title compound (2.03 g, 4.1 mmol, 100%).
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:15][CH2:14][S:13][CH2:12]2)=[C:4](Cl)[N:3]=1.C(O)CCC.[CH2:22]([NH2:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C(O)(C)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:15][CH2:14][S:13][CH2:12]2)=[C:4]([NH:29][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:3]=1
Reactant: Clc1nc(Cl)c2ncn(C3CCSC3)c2n1
Reactant: NCc1ccccc1
Solvent: CCCCO
Solvent: CC(C)O
Product: Clc1nc(NCc2ccccc2)c2ncn(C3CCSC3)c2n1
Temperature: 97.5 °C

Procedure:
120 mg of the product obtained in Stage 1 above, 2 ml of butanol and 0,105 ml of benzylamine are mixed together and the reaction medium is heated to a temperature of approximately 95 to 100° C. for 10 hours. It is then left to return to ambient temperature and diluted with 5 ml of isopropanol, followed by separating, washing with 5 ml of isopropanol and drying under vacuum at approximately 30° C. In this way 132 mg of expected product is obtained in the form of white crystals.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([S:19][CH:20]([C:31]2[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=2[F:38])[C:21]2[C:22]([CH3:30])=[CH:23][C:24]([C:27]([NH2:29])=[O:28])=[N:25][CH:26]=2)=[CH:15][CH:14]=1>C(Cl)Cl>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([S:19]([CH:20]([C:31]2[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=2[F:38])[C:21]2[C:22]([CH3:30])=[CH:23][C:24]([C:27]([NH2:29])=[O:28])=[N:25][CH:26]=2)=[O:9])=[CH:15][CH:14]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1cc(C(N)=O)ncc1C(Sc1ccc(Cl)cc1)c1cc(F)ccc1F
Solvent: ClCCl
Product: Cc1cc(C(N)=O)ncc1C(c1cc(F)ccc1F)S(=O)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 336 h
Yield: 59.2 %

Procedure:
3-Chloroperbenzoic acid (259 mg, 0.98 mmol) was added to a solution of 5-[[(4-chlorophenyl)thio](2,5-difluorophenyl)methyl]-4-methylpyridine-2-carboxamide (395 mg, 0.98 mmol) in methylene chloride (10 ml) at 0° C. After stirring for 14 days at room temperature, the reaction mixture was washed with 1 N aqueous sodium hydroxide. The organic layer was dried over anhydrous sodium sulfate and filtered, then the filtrate was concentrated under reduced pressure, and the resulting residue was subjected to flash silica gel chromatography. The fraction obtained from an elution with hexane:ethyl acetate=1:1 was concentrated under reduced pressure, and the resulting residue was washed with a mixed solvent of ethanol and diethyl ether, and collected by filtration, thus to obtain the title compound (243 mg, 0.58 mmol, 59%) as a white solid.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].C[O:8][C:9](=O)[CH2:10][C:11]1[CH:16]=[C:15]([Cl:17])[C:14]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)=[CH:13][C:12]=1[O:24][CH3:25].C(OCC)(=O)C>O1CCCC1>[Cl:17][C:15]1[C:14]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)=[CH:13][C:12]([O:24][CH3:25])=[C:11]([CH2:10][CH2:9][OH:8])[CH:16]=1
Reactant: COC(=O)Cc1cc(Cl)c(C2CCCCC2)cc1OC
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: COc1cc(C2CCCCC2)c(Cl)cc1CCO
Reaction time: 18 h

Procedure:
7 g of LiAlH4 are added in portions at 0° under an inert gas atmosphere to 16 g of (5-chloro-4- cyclohexyl-2-methoxyphenyl)-acetic acid methyl ester in 350 ml of dry tetrahydrofuran. Stirring is then effected for 18 hours at 22° . 20 ml of ethyl acetate are carefully added in drops so as to destroy the excess LiAlH4. The mixture is then poured onto a solution of NH4Cl in ice water, acidified with 2N H2SO4 and extracted three times with acetic ester. The organic phases are washed with water, dried over Na2SO4 and concentrated. The residue is chromatographed on 250 g of silica gel. The product, which is extracted with methylene chloride, is distilled in a bulb tube. M.p. 78°-79°.
Reaction SMILES: [C:1]([O:5][C:6](=[O:49])[CH2:7][N:8]([C:18](=[O:48])[C@H:19]([CH3:47])[NH:20][C@H:21]([C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:22][CH2:23][CH2:24][CH2:25][CH:26]1[CH2:31][CH2:30][N:29](C(OCC2C=CC=CC=2)=O)[CH2:28][CH2:27]1)[CH:9]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH2:10]1)([CH3:4])([CH3:3])[CH3:2]>CO.[C].[Pd]>[C:1]([O:5][C:6](=[O:49])[CH2:7][N:8]([C:18](=[O:48])[C@H:19]([CH3:47])[NH:20][C@H:21]([C:42]([O:44][CH2:45][CH3:46])=[O:43])[CH2:22][CH2:23][CH2:24][CH2:25][CH:26]1[CH2:27][CH2:28][NH:29][CH2:30][CH2:31]1)[CH:9]1[CH2:10][C:11]2[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:17]1)([CH3:3])([CH3:2])[CH3:4]
Reactant: CCOC(=O)[C@H](CCCCC1CCN(C(=O)OCc2ccccc2)CC1)N[C@@H](C)C(=O)N(CC(=O)OC(C)(C)C)C1Cc2ccccc2C1
Agent: [Pd]
Solvent: CO
Product: CCOC(=O)[C@H](CCCCC1CCNCC1)N[C@@H](C)C(=O)N(CC(=O)OC(C)(C)C)C1Cc2ccccc2C1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
In 20 ml of methanol is dissolved 0.4 g of N-[N-[(S)-5-(1-benzyloxycarbonyl-4-piperidyl)-1-ethoxycarbonylpentyl]-L-alanyl]-N-(indan-2-yl)glycine tert-butyl ester, and a catalytic reduction is carried out at ambient temperature and under atmospheric pressure using 10% palladium-carbon (50% wet, 0.4 g) as a catalyst. After stirring at room temperature for 4 hours, the catalyst is removed by filtration, and the filtrate is concentrated under reduced pressure to give 0.3 of N-[N-[(S)-5-(4-piperidyl)-1-ethoxycarbonylpentyl]-L-alanyl]-N-(indan-2-yl)glycine tert-butyl ester as a colorless oil.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].Br[CH:13]([CH3:15])[CH3:14].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH:13]([N:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]1=[O:1])([CH3:15])[CH3:14]
Reactant: COC(=O)c1ccnc(O)c1
Reactant: CC(C)Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1ccn(C(C)C)c(=O)c1
Temperature: 110 °C
Reaction time: 8 h
Yield: 17.9 %

Procedure:
To a solution of methyl 2-hydroxyisonicotinate (306 mg, 2 mmol) in dimethyl formamide (30 mL) was added 2-bromopropane (0.24 g, 2 mmol) and potassium carbonate (5.52 g, 4 mmol), the mixture was heated to 110° C. and stirred overnight. The solvent was evaporated in vacuo and purified by column chromatography (silica gel, petroleum ether/ethyl acetate=3:1) to give methyl 1-isopropyl-2-oxo-1,2-dihydropyridine-4-carboxylate (70 mg, 18%). LRMS (M+H+) m/z: calcd 195.05. found 195.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[CH:6]=[CH:5]2.[Cl-].[Al+3].[Cl-].[Cl-].[Br:17]Br.Cl>ClCCCl.O>[Br:17][C:3]1[C:2]([F:1])=[CH:11][CH:10]=[C:9]2[C:4]=1[CH:5]=[CH:6][C:7]([CH3:12])=[N:8]2
Reactant: Cc1ccc2cc(F)ccc2n1
Reactant: BrBr
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: ClCCCl
Product: Cc1ccc2c(Br)c(F)ccc2n1
Temperature: 75 °C
Reaction time: 0.25 h
Yield: 99.2 %

Procedure:
A solution of 12.1 kg (75 mole) of 6-fluoro-2-methylquinoline in 33 liters of 1,2-dichloroethane was chilled to 5° C., and 15.0 kg (113 mole) of aluminum chloride was added thereto in portions over 15 minutes. The mixture was purged with nitrogen and then heated to 75° C. A solution of 13.2 kg (82.6 mole) of bromine in 2 liters of 1,2-dichloroethane was added over a period of 5.5 hours. The reaction was maintained at 75° C. during the addition and for an additional 15 minutes after the addition was completed. The reaction was stirred at 70° C. for 23 hours and was then cooled to 10° C. and slowly added to a mixture of 8 kg of 30% hydrochloric acid, 41 liters of water and 31.75 kg of ice. The mixture warmed to 50° C. during the addition. The mixture was heated in reflux and the 1,2-dichloroethane was removed by azeotropic distillation. The remaining aqueous solution was cooled to 60° C. and 12 kg of 10% hydrochloric acid was added. The solution was treated with Celite® (available from Johns-Manville Corp.) and filtered. The filtrate was cooled to 25° C. and 18 kg of 30% hydrochloric acid and 10.22 kg of zinc chloride were added. The resulting slurry was chilled to 5° C. and allowed to stir for several days. The solid was collected and then reslurried with 10 gallons of water. The slurry was chilled to 5° C. and 22 kg of chilled ammonium hydroxide was added. The resulting slurry (pH 10-11) was diluted with 25 gallons of water and the solid was collected, rinsed with water and dried in vacuo at 60° C. to give crude 5-bromo-6-fluoro-2-methylquinoline (84.5% pure by gas chromatography analysis). The material was recrystallized from hexane to give 99.2% pure 5-bromo-6-fluoro-2-methylquinoline.
Reaction SMILES: C([NH:4][C:5]1[CH:6]=[C:7]2[S:13][CH:12]=[CH:11][C:8]2=[N:9][CH:10]=1)(=O)C.[OH-].[Na+]>C(O)C.Cl.O>[NH2:4][C:5]1[CH:6]=[C:7]2[S:13][CH:12]=[CH:11][C:8]2=[N:9][CH:10]=1
Reactant: CC(=O)Nc1cnc2ccsc2c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Nc1cnc2ccsc2c1
Temperature: 80 °C
Yield: 75.5 %

Procedure:
A suspension of 6-acetamidothieno[3,2-b]pyridine (2.29 g, 12 mmol) in ethanol (35 ml) and concentrated hydrochloric acid (15 ml) was warmed at 80° C. for two hours. This mixture was diluted with water and made basic by the addition of sodium hydroxide solution. The product was extracted into methylene chloride, dried over anhydrous sodium sulfate and then filtered through a pad of charcoal and the solvent was evaporated to give pure product (1.36 g, 76% yield), m.p. 121°-123° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=O)[CH:5]=[CH:6][CH:7]=1.[NH2:12][CH:13]([CH2:21][CH3:22])[C:14]([O:16][CH2:17][CH:18]([CH3:20])[CH3:19])=[O:15]>>[CH2:17]([O:16][C:14](=[O:15])[CH:13]([NH:12][C:9](=[O:11])[CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=1)[CH2:21][CH3:22])[CH:18]([CH3:19])[CH3:20]
Reactant: O=C(O)Cc1cccc(Cl)c1
Reactant: CCC(N)C(=O)OCC(C)C
Product: CCC(NC(=O)Cc1cccc(Cl)c1)C(=O)OCC(C)C

Procedure:
Following General Procedure I′ above and using 3-chlorophenylacetic acid (Aldrich) and iso-butyl 2-aminobutyrate (prepared following General Procedure J′ above), the title compound was prepared. The reaction was monitored by tlc on silica gel and purification was by filtration as described in the general procedure.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][N:9]2[C:13]3[CH:14]=[CH:15][C:16](B4OC(C)(C)C(C)(C)O4)=[CH:17][C:12]=3[NH:11][C:10]2=[O:27])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.Br[CH:29]=[C:30]1[C:36]2[CH:37]=[CH:38][C:39]([F:41])=[CH:40][C:35]=2[CH2:34][CH2:33][C:32]2[CH:42]=[C:43]([F:46])[CH:44]=[CH:45][C:31]1=2.C([O-])([O-])=O.[Na+].[Na+]>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.O1CCOCC1>[F:41][C:39]1[CH:38]=[CH:37][C:36]2[C:30](=[CH:29][C:16]3[CH:15]=[CH:14][C:13]4[N:9]([CH2:8][CH2:7][N:1]5[CH2:2][CH2:3][O:4][CH2:5][CH2:6]5)[C:10](=[O:27])[NH:11][C:12]=4[CH:17]=3)[C:31]3[CH:45]=[CH:44][C:43]([F:46])=[CH:42][C:32]=3[CH2:33][CH2:34][C:35]=2[CH:40]=1
Reactant: CC1(C)OB(c2ccc3c(c2)[nH]c(=O)n3CCN2CCOCC2)OC1(C)C
Reactant: Fc1ccc2c(c1)CCc1cc(F)ccc1C2=CBr
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: O=c1[nH]c2cc(C=C3c4ccc(F)cc4CCc4cc(F)ccc43)ccc2n1CCN1CCOCC1
Yield: 45.4 %

Procedure:
Following procedures essentially as described in Example 219, mix 1-(2-morpholin-4yl-ethyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-benzoimidazol-2-one (520 mg, 1.4 mmol), 5-bromomethylene-2,8-difluoro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (510 mg, 1.6 mmol)(prepared using a procedure essentially as described for the 2,8-dichloro derivative in Example 182), 2N Na2CO3 (1 mL), dioxane (10 mL) and (Ph3P)4Pd (67 mg, 0.06 mmol). Purify the crude product by column chromatography using MeOH/ethyl acetate to give 310 mg colorless oil that solidified upon drying, HPLC (ISO80-10M) t=2.03 (97%). MS (ES) 488 (M+1), 486 (M−1). H NMR 10.69 (s, 1H), 7.49 (dd, 1H, J=8.4, 6.2 Hz), 7.22 (dd, 1H, J=9.7, 2.2 Hz), 7.02 (td, 1H, J=12.0, 4.2 Hz), 6.97-6.83 (m, 4H), 6.81 (s, 1H), 6.72 (d, 1H, J=7.9 Hz), 6.56 (s, 1H), 3.80 (t, 2H, J=6.2 Hz), 3.47 (t, 4H, J=4.2 Hz), 3.31 (s, 2H), 2.90 (s, 2H), 2.48 (m, 2H), 2.38 (s, 4H).
Reaction SMILES: O[C:2]([C:13]1[C:21]2[O:20][CH2:19][CH2:18][C:17]=2[C:16]([CH3:22])=[C:15]([NH:23][C:24](=O)[O:25]C(C)(C)C)[C:14]=1[CH3:31])([C:4]1[CH:9]=[CH:8][C:7]([CH:10]([CH3:12])[CH3:11])=[CH:6][CH:5]=1)[CH3:3].[C:32]([CH2:36]C(Cl)=O)([CH3:35])([CH3:34])[CH3:33]>C(OCC)(=O)C.CCCCCC>[CH:10]([C:7]1[CH:6]=[CH:5][C:4]([CH:2]([C:13]2[C:21]3[O:20][CH2:19][CH2:18][C:17]=3[C:16]([CH3:22])=[C:15]([NH:23][C:24](=[O:25])[CH2:33][C:32]([CH3:36])([CH3:35])[CH3:34])[C:14]=2[CH3:31])[CH3:3])=[CH:9][CH:8]=1)([CH3:12])[CH3:11]
Reactant: Cc1c2c(c(C(C)(O)c3ccc(C(C)C)cc3)c(C)c1NC(=O)OC(C)(C)C)OCC2
Reactant: CC(C)(C)CC(=O)Cl
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: Cc1c2c(c(C(C)c3ccc(C(C)C)cc3)c(C)c1NC(=O)CC(C)(C)C)OCC2
Yield: 61 %

Procedure:
Using tert-butyl (7-(1-hydroxy-1-(4-isopropylphenyl)ethyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-yl)carbamate obtained in Example 223 and tert-butylacetyl chloride, the title compound was synthesized in the same manner as in Example 224. Yield: 61%. Melting point: 189-190° C. (ethyl acetate-hexane).
Reaction SMILES: [I-].[K+].C[Si](Cl)(C)C.[CH2:8]([O:15][CH2:16][C:17]1[N:18]([CH2:34][C:35]2[CH:36]=[CH:37][C:38]([O:41]C)=[N:39][CH:40]=2)[C:19]([S:25][C:26]2[CH:31]=[C:30]([Cl:32])[CH:29]=[C:28]([Cl:33])[CH:27]=2)=[C:20]([CH:22]([CH3:24])[CH3:23])[N:21]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C(#N)C>[CH2:8]([O:15][CH2:16][C:17]1[N:18]([CH2:34][C:35]2[CH:36]=[CH:37][C:38](=[O:41])[NH:39][CH:40]=2)[C:19]([S:25][C:26]2[CH:27]=[C:28]([Cl:33])[CH:29]=[C:30]([Cl:32])[CH:31]=2)=[C:20]([CH:22]([CH3:24])[CH3:23])[N:21]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: COc1ccc(Cn2c(COCc3ccccc3)nc(C(C)C)c2Sc2cc(Cl)cc(Cl)c2)cn1
Agent: C[Si](C)(C)Cl
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Product: CC(C)c1nc(COCc2ccccc2)n(Cc2ccc(=O)[nH]c2)c1Sc1cc(Cl)cc(Cl)c1
Temperature: 60 °C
Reaction time: 0.17 h
Yield: 34.2 %

Procedure:
To a solution of 83 mg of potassium iodide in acetonitrile was added 64 μl of trimethylsilyl chloride under ice-cooling and stirring. The mixture was allowed to warm up, and after 10 minutes, 150 mg of 2-benzyloxymethyl-5-(3,5-dichlorophenylthio)-1-(2-methoxypyridin-5-ylmethyl)-4-isopropyl-1H-imidazole was added, and the mixture was stirred with heating at 60° C. After 1 hour, the solution was distilled off under reduced pressure, an aqueous sodium hydrogen carbonate solution was added, extracted with ethyl acetate, the extract was dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate: methanol=10:1) to give 50 mg of 2-benzyloxymethyl-5-(3,5-dichlorophenylthio)-1-(6-oxo-1,6-dihydro-pyridin-3-yl)methyl-4-isopropyl-1H-imidazole (115a) (yield 34%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11](O)([CH3:22])[CH2:12][CH2:13][CH2:14][CH2:15][C:16]#[C:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.C(Cl)(Cl)(Cl)[Cl:25]>>[Cl:25][C:11]([C:5]1[CH:4]=[C:3]([O:2][CH3:1])[CH:8]=[C:7]([O:9][CH3:10])[CH:6]=1)([CH3:22])[CH2:12][CH2:13][CH2:14][CH2:15][C:16]#[C:17][Si:18]([CH3:21])([CH3:20])[CH3:19]
Reactant: COc1cc(OC)cc(C(C)(O)CCCCC#C[Si](C)(C)C)c1
Reactant: ClC(Cl)(Cl)Cl
Product: COc1cc(OC)cc(C(C)(Cl)CCCCC#C[Si](C)(C)C)c1

Procedure:
The above carbinol (1 equiv.) was dissolved in anhydrous carbon tetrachloride (0.5 M) and dry hydrogen chloride gas was bubbled through for 1 hour. The solution was transferred to a separatory funnel with the aid of more carbon tetrachloride, washed with water and 10% sodium bicarbonate solution. The organic phase was dried and rotary evaporated to afford an oil which was passed through a short silica gel column to give pure [7-chloro-7-(3,5-dimethoxyphenyl)-1-octynyl]trimethylsilane.
Reaction SMILES: C(OC([NH:8][CH2:9][CH2:10][O:11][C:12](=[O:29])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[NH:20][C:21]1[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=1[Cl:28])=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][CH2:9][CH2:10][O:11][C:12](=[O:29])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[NH:20][C:21]1[C:26]([Cl:27])=[CH:25][CH:24]=[CH:23][C:22]=1[Cl:28]
Reactant: CC(C)(C)OC(=O)NCCOC(=O)Cc1ccccc1Nc1c(Cl)cccc1Cl
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: NCCOC(=O)Cc1ccccc1Nc1c(Cl)cccc1Cl
Temperature: 25 °C
Reaction time: 16 h
Yield: 24.4 %

Procedure:
To a stirred solution of [2-(2,6-Dichloro-phenylamino)-phenyl]-acetic acid 2-tert-butoxycarbonylamino-ethyl ester 4 (5.3 g, 0.01 mol) in DCM (50 mL) was added TFA (5.3 mL) at 0° C. The resulting mixture was stirred at room temperature for 16 h. Reaction was monitored by TLC. After completion, reaction mixture was concentrated under reduced pressure. The residue was neutralized with aq sodium bicarbonate and extracted with DCM (2×50 mL). Combined organic layer was dried over anhy Na2SO4 and evaporated under reduced pressure. Crude compound was purified by silica gel column chromatography using methanol and DCM (5:95) to get 1.0 g (24.4% Yield) Compound-5 as a brown solid; Mass: 339.0 (M++H).
Reaction SMILES: Cl[CH:2]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[NH:9][C:8](=[O:13])[NH:7][CH2:6]2.[NH:20]1[CH:24]=[CH:23][N:22]=[CH:21]1.C(#N)C>CS(C)=O>[N:20]1([CH:2]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:3]2[CH:4]=[C:5]3[C:10](=[CH:11][CH:12]=2)[NH:9][C:8](=[O:13])[NH:7][CH2:6]3)[CH:24]=[CH:23][N:22]=[CH:21]1
Reactant: c1c[nH]cn1
Reactant: O=C1NCc2cc(C(Cl)c3ccccc3)ccc2N1
Solvent: CS(C)=O
Solvent: CC#N
Product: O=C1NCc2cc(C(c3ccccc3)n3ccnc3)ccc2N1
Reaction time: 4 h
Yield: 58.1 %

Procedure:
A mixture of 3.6 parts of 6-(chlorophenylmethyl)-3,4-dihydro-2(1H)-quinazolinone, 5.3 parts of 1H-imidazole, 60 parts of acetonitrile and 27.5 parts of dimethyl sulfoxide was stirred for 4 hours at reflux temperature. After concentration, the residue was washed twice with water, dissolved in a mixture of trichloromethane and methanol (90:10 by volume), dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a 45 parts of ethyl acetate and a few drops of water. The product was filtered off, washed with ethyl acetate and 2,2'-oxybispropane and dried, yielding 2.3 parts (58.1%) of 3,4-dihydro-6-[(1H-imidazol-1-yl)phenylmethyl]-2(1H)-quinazolinone; mp. 222.5° C. (comp. 16).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[NH:10][CH:11]=[C:12]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=2)[N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[CH:30]=[C:29]([S:34]([N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)(=[O:36])=[O:35])[CH:28]=[CH:27]2>C(O)C>[Br:23][C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[CH:30]=[C:29]([S:34]([N:37]1[CH2:38][CH2:39][N:40]([C:18](=[O:20])[C:17]3[CH:21]=[CH:22][C:14]([C:12]4[N:13]=[C:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[NH:10][CH:11]=4)=[CH:15][CH:16]=3)[CH2:41][CH2:42]1)(=[O:35])=[O:36])[CH:28]=[CH:27]2
Reactant: CC(C)(C)OC(=O)Nc1nc(-c2ccc(C(=O)O)cc2)c[nH]1
Reactant: O=S(=O)(c1ccc2cc(Br)ccc2c1)N1CCNCC1
Solvent: CCO
Product: CC(C)(C)OC(=O)Nc1nc(-c2ccc(C(=O)N3CCN(S(=O)(=O)c4ccc5cc(Br)ccc5c4)CC3)cc2)c[nH]1

Procedure:
The requisite 1-(6-bromonaphth-2-ylsulphonyl)-4-[4-(2-t-butyloxycarbonylaminoimidazol-4-yl)benzoyl]piperazine starting material was prepared by a coupling method exactly analogous to that described in Example 1, starting from 4(2-t-butyloxycarbonylaminoimidazol-4-yl)benzoic acid and 1-(6-bromonaphth-2-ylsulphonyl)piperazine, to give 1-(6-bromonaphth-2-ylsulphonyl)-4-[4-(2-t-butyloxycarbonylaminoimidazol-4-yl)benzoyl]piperazine as a colourless solid (after trituration with hot ethanol) (248 mg, 40% yield), m.p. 175-177° C., 1H NMR (d6DMSO) 1.5 ppm (s,9H), 3.0-3.1 ppm (broad s,4H), 3.4-3.7 ppm (broad s,4H), 6.6 ppm (s,2H), 7.3 ppm (d,2H), 7.4 ppm (s,1H), 7.7 ppm (d,2H), 7.8 ppm (t,2H), 8.2 ppm (t,2H), 8.4 ppm (s,1H), 8.45 ppm (s,1H); MS (M+H)+ 640/642 (w), (M+H-56)+ 584/585 (s), loss of C4H8.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:19])[C:5]1[CH:10]=[CH:9][C:8]([N:11]2[CH:15]=[C:14]([OH:16])[C:13]([C:17]#[N:18])=[CH:12]2)=[CH:7][CH:6]=1)[CH3:2].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[CH2:1]([O:3][C:4](=[O:19])[C:5]1[CH:6]=[CH:7][C:8]([N:11]2[CH:12]=[C:13]([C:17]#[N:18])[C:14]([O:16][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:15]2)=[CH:9][CH:10]=1)[CH3:2]
Reactant: CCOC(=O)c1ccc(-n2cc(O)c(C#N)c2)cc1
Reactant: BrCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1ccc(-n2cc(C#N)c(OCc3ccccc3)c2)cc1
Temperature: 80 °C
Reaction time: 5 h
Yield: 22.8 %

Procedure:
To a solution of 4-(3-cyano-4-methoxypyrrole-1-yl)benzoic acid ethyl ester (0.081 g) in dichloromethane (3 mL) was added boron tribromide (0.33 mL, 1 mol/L dichloromethane solution) under ice-cooling, and this mixture was stirred at same temperature for 2 hours. To this reaction mixture was added water, and this mixture was extracted with diethyl ether. This organic layer was washed with brine, dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/n-hexane=1/1) to give 4-(3-cyano-4-hydroxypyrrole-1-yl)benzoic acid ethyl ester (0.052 g). To a solution of 4-(3-cyano-4-hydroxypyrrole-1-yl)benzoic acid ethyl ester (0.052 g) in N,N-dimethylformamide (4 mL) were added benzylbromide (0.038 g) and cesium carbonate (0.13 g) at room temperature, and this mixture was stirred at 80° C. for 5 hours. To this reaction mixture was added water at room temperature, and the precipitated solid was collected by filtration, and washed with methanol (5 mL) to give the title compound (0.016 g).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[OH:9].[CH2:10]([C:13]1[N:17]=[C:16]([CH2:18]Cl)[O:15][N:14]=1)[CH:11]=[CH2:12].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:10]([C:13]1[N:17]=[C:16]([CH2:18][O:9][C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[Cl:1])[O:15][N:14]=1)[CH:11]=[CH2:12]
Reactant: Oc1ccc(F)cc1Cl
Reactant: C=CCc1noc(CCl)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C=CCc1noc(COc2ccc(F)cc2Cl)n1
Yield: 80.7 %

Procedure:
0.71 g of 2-chloro-4-fluorophenol, 0.77 g of 3-allyl-5-chloromethyl-1,2,4-oxadiazole and 0.83 of potassium carbonate were added to 20 ml of acetone. After completion of the reaction, the resulting precipitates were filtered out from the mixture and then acetone was removed by distillation, and the residue was purified by column chromatography (benzene:hexane=1:1) to obtain 1.05 g of the desired product(yield: 80.8%).