Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][C@@H:3]([NH:6][C:7](=[O:22])[CH2:8][C:9]2[NH:13][C:12]3[CH:14]=[CH:15][CH:16]=[C:17]([C:18]([F:21])([F:20])[F:19])[C:11]=3[N:10]=2)[CH2:2]1.[O:23]1[CH2:28][CH2:27][C:26](=O)[CH2:25][CH2:24]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([O-])(O)=O.[Na+]>CO.ClCCl>[O:23]1[CH2:28][CH2:27][CH:26]([N:1]2[CH2:5][CH2:4][C@@H:3]([NH:6][C:7](=[O:22])[CH2:8][C:9]3[NH:10][C:11]4[C:17]([C:18]([F:19])([F:20])[F:21])=[CH:16][CH:15]=[CH:14][C:12]=4[N:13]=3)[CH2:2]2)[CH2:25][CH2:24]1
Reactant: O=C(Cc1nc2c(C(F)(F)F)cccc2[nH]1)N[C@@H]1CCNC1
Reactant: O=C1CCOCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: ClCCl
Product: O=C(Cc1nc2cccc(C(F)(F)F)c2[nH]1)N[C@@H]1CCN(C2CCOCC2)C1
Reaction time: 16 h

Procedure:
To a solution of N-[(3R)-pyrrolidin-3-yl]-2-[4-(trifluoromethyl)-1H-benzimidazol-2-yl]acetamide (1.0 equiv) in methanol (0.500 M) at room temperature was added tetrahydro-4H-pyran-4-one (1.25 equiv.) followed by sodium triacetoxyborohydride (4 equiv); the reaction mixture was stirred for 16 hours. To the mixture was added NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL). The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to flash chromatography (15% MeOH, 1% NH4OH in EtOAc) to afford N-[(3R)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]-2-[7-(trifluoromethyl)-1H-benzimidazol-2-yl]acetamide as a white solid. 1H-NMR (CD3Cl3) δ: 1.45-1.74 (m, 5H), 2.14-2.22 (m, 2H), 2.33 (m, 1H), 2.60 (m, 2H), 2.83 (m, 1H), 3.34 (m, 2H), 3.91 (m, 2H), 3.95 (s, 2H), 4.39 (m, 1H), 7.27 (t, J=8.0 Hz, 1H), 4.45-7.54 (m, 2H). MS m/z: 397 (M+1).
Reaction SMILES: [O:1]=[C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[S:5][C:4]([C:12]2[N:17]=[C:16](/[CH:18]=[CH:19]/[C:20]([O:22]C(C)(C)C)=[O:21])[CH:15]=[CH:14][CH:13]=2)=[N:3]1>FC(F)(F)C(O)=O>[O:1]=[C:2]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[S:5][C:4]([C:12]2[N:17]=[C:16](/[CH:18]=[CH:19]/[C:20]([OH:22])=[O:21])[CH:15]=[CH:14][CH:13]=2)=[N:3]1
Reactant: CC(C)(C)OC(=O)/C=C/c1cccc(-c2nc(=O)c3ccccc3s2)n1
Solvent: O=C(O)C(F)(F)F
Product: O=C(O)/C=C/c1cccc(-c2nc(=O)c3ccccc3s2)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 96.7 %

Procedure:
tert-Butyl (E)-3-[6-(4-oxo-4H-1,3-benzothiazin-2-yl)-2-pyridyl]-2-propenoate (0.78 g, 2.0 mmol) was dissolved in trifluoroacetic acid (4.0 ml) under ice cooling condition. The reaction mixture was stirred for 1 hr while it was warmed gradually to room temperature. The reaction mixture was concentrated under reduced pressure to precipitate crystals, which were recrystallized from methanol-diisopropyl ether to give the titled compound (0.60 g, 97%) as white crystals.
Reaction SMILES: [C:1]1([C:7](=O)[CH3:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1.[CH3:10][O:11][NH2:12]>C(O)(=O)C>[CH3:10][O:11][N:12]=[C:7]([C:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]=1)[CH3:8]
Reactant: CON
Reactant: CC(=O)C1=CCCCC1
Solvent: CC(=O)O
Product: CON=C(C)C1=CCCCC1
Temperature: 24 °C
Reaction time: 48 h

Procedure:
To a stirred solution of a cyclohexenyl-ethanone (0.06 mmol), in acetic acid (500 μl) was added methoxyamine (4.7 mg). The reaction mixture was stirred at 24° C. for 48 h under nitrogen to obtain the cyclohexenyl-ethanone O-methyl-oxime.
Reaction SMILES: [Cl-].[CH3:2][O:3][C:4](=[O:12])[CH2:5][CH2:6][CH2:7][CH2:8][C:9]([OH:11])=O.[Al](Cl)(Cl)Cl.[Cl:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>>[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C:9]([CH2:8][CH2:7][CH2:6][CH2:5][C:4]([O:3][CH3:2])=[O:12])=[O:11])=[CH:20][CH:19]=1
Reactant: Clc1ccccc1
Reactant: COC(=O)CCCCC(=O)O
Agent: Cl[Al](Cl)Cl
Agent: [Cl-]
Product: COC(=O)CCCCC(=O)c1ccc(Cl)cc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
Adipic acid monomethyl ester chloride (17.9 g) was added dropwise into a mixture of chlorobenzene(33.8 g) and aluminum chloride anhydrous(26.7 g) with cooling with ice. After stirring for 2 hours, the reaction mixture was poured into ice water, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, and dried (MgSO4). The solvent was evaporated to give methyl 5-(4-chlorobenzoyl)pentanoate. This was dissolved into dichloromethane(100 ml), thereto bromine(16.0 g) was added dropwise. The reaction mixture was washed with water and then with sodium hydrogensulfite. The dichloromethane layer was washed with water, and dried (MgSO4). The solvent was evaporated to give methyl 5-bromo-5-(4-chlorobenzoyl)pentanoate(31.7 g, 95%) as an oily substance.
Reaction SMILES: [F:1][C:2]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([O:15]CC)=[O:14])[CH:9]=[CH:10][CH:11]=1.[OH-].[Na+]>C(O)C>[F:1][C:2]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:3]=1[CH2:4][O:5][C:6]1[CH:7]=[C:8]([CH2:12][C:13]([OH:15])=[O:14])[CH:9]=[CH:10][CH:11]=1
Reactant: CCOC(=O)Cc1cccc(OCc2c(F)cccc2F)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)Cc1cccc(OCc2c(F)cccc2F)c1
Reaction time: 3 h

Procedure:
To a stirred solution Ethyl 2-(3-(2,6-difluorobenzyloxy)phenyl)acetate (Step B, 7.86 g, 24 mmol) in absolute ethanol (120 ml) was added 1N NaOH (50 ml) at room temperature. The reaction mixture was stirred for 3 hours, or until all the starting material is gone, concentrated and diluted with chloroform and washed with 1M HCl to bring the pH to 3.5-4. The organic layer was washed with brine, dried over Na2SO4, filtered, concentrated and purified by flash chromatography on a silica gel column (chloroform:methanol, 95:5 spiked with acetic acid) to give the title compound as white solid.
Reaction SMILES: [H-].[Na+].[CH2:3]([N:5]([CH2:17][CH3:18])[C:6](=[O:16])[CH2:7]P(=O)(OCC)OCC)[CH3:4].[F:19][C:20]1[CH:47]=[CH:46][CH:45]=[C:44]([F:48])[C:21]=1[CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:30](=O)[CH3:31])=[CH:26][C:25]=1[O:33][CH2:34][CH2:35][CH2:36][O:37][CH:38]1[CH2:43][CH2:42][CH2:41][CH2:40][O:39]1>C1COCC1>[CH2:17]([N:5]([CH2:3][CH3:4])[C:6](=[O:16])/[CH:7]=[C:30](/[C:27]1[CH:28]=[CH:29][C:24]([O:23][CH2:22][C:21]2[C:20]([F:19])=[CH:47][CH:46]=[CH:45][C:44]=2[F:48])=[C:25]([O:33][CH2:34][CH2:35][CH2:36][O:37][CH:38]2[CH2:43][CH2:42][CH2:41][CH2:40][O:39]2)[CH:26]=1)\[CH3:31])[CH3:18]
Reactant: CC(=O)c1ccc(OCc2c(F)cccc2F)c(OCCCOC2CCCCO2)c1
Reactant: CCOP(=O)(CC(=O)N(CC)CC)OCC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCN(CC)C(=O)/C=C(\C)c1ccc(OCc2c(F)cccc2F)c(OCCCOC2CCCCO2)c1
Temperature: 25 °C
Reaction time: 0.08 h

Procedure:
To a solution of washed NaH (0.74 g, 30.94 mmol)) in THF (30 mL) is added a solution of diethyl [2-(diethylamino)-2-oxoethyl]-phosphonate (7.77 g, 30.94 mmol) in THF (30 mol), dropwise, and the solution is stirred at room temperature for 5 minutes until gas evolution ceases. A solution of 4′-(2,6-difluorobenzyloxy)-3′-[3-(tetrahydropyran-2-yloxy)-propoxy]-acetophenone (6.50 g, 15.47 mmol) in THF (30 mL) is then added over 5 minutes and the resulting mixture is refluxed for 18 hours. After cooling, the mixture is quenched with 30 mL saturated aqueous NH4Cl, and is concentrated to 30 mL in vacuo. The residue is dissolved in EtOAc (50 mL), washed with H2O (1×50 mL) and brine (1×50 ml), dried over MgSO4, and concentrated in vacuo. Chromatography (silica, 3:1 hexane/EtOAc) provides N,N-diethyl (E)-3-{4-(2,6-difluorobenzyloxy)-3-[3-(tetrahydropyran-2-yloxy)-propoxy]-phenyl}-2-butenamide.
Reaction SMILES: [F:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].C(Cl)(=O)C([Cl:14])=O>C1COCC1.CN(C=O)C>[F:1][C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([Cl:14])=[O:5]
Reactant: O=C(O)c1cccnc1F
Reactant: O=C(Cl)C(=O)Cl
Solvent: C1CCOC1
Solvent: CN(C)C=O
Product: O=C(Cl)c1cccnc1F

Procedure:
A homogeneous mixture of 2-fluoronicotinic acid (Aldrich, 0.45 g, 3.2 mmol), in anhydrous THF (12 mL), was treated with oxalyl chloride (0.56 mL, 6.4 mmol) followed by anhydrous DMF (2 drops). After heating at reflux for 1.5 hours, the reaction mixture was concentrated in vacuo to afford 2-fluoronicotinoyl chloride as a residue which was used without further purification. The residue was dissolved in anhydrous THF (8 mL), anhydrous DCM (2 mL), pyridine (1 mL) and DMF (to a total volume of 16 mL). This homogeneous 2-fluoronicotinoyl chloride mixture (2 mL) was then added to a rapidly stirred mixture of o-toluidine (Aldrich, 0.17 mL, 1.6 mmol) in anhydrous THF (2 mL). After 15 hours, the reaction was quenched with water, and then extracted with 10% isopropanol in chloroform. The organic layer was washed once with sat. aq. NaHCO3, once with sat. aq. NaCl, then dried over anhydrous Na2SO4 and concentrated in vacuo to afford the desired product (0.084 g, 91%) as a pale orange solid which was used without further purification. MS(ESI+) m/z 231 (M+H)+.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([SH:19])[CH:13]=[CH:12]2.BrC1C=C2C(=CC=1)C=C(O)C=C2.[C:32](#[N:35])[CH:33]=[CH2:34].C(N(CC)CC)C>O1CCCC1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([S:19][CH2:34][CH2:33][C:32]#[N:35])[CH:13]=[CH:12]2
Reactant: Fc1ccc(-c2ccc3cc(S)ccc3c2)c(F)c1
Reactant: C=CC#N
Agent: Oc1ccc2cc(Br)ccc2c1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: N#CCCSc1ccc2cc(-c3ccc(F)cc3F)ccc2c1
Temperature: 50 °C

Procedure:
A mixture of 6-(2,4-difluorophenyl)-2-naphthyl hydrosulfide (prepared from 6-bromo-2-naphthol according to the methods of Example 1 Steps 1 and 2 and Example 2 Step 2, 7.3 g, 24.7 mmol), acrylonitrile (2.6 mL, 39.5 mmol) and triethylamine (370 μL) in tetrahydrofuran (50 mL) was heated to 50° C. under nitrogen for 1 hour. The solvent was removed in vacuo. The residue was triturated with isohexane to give 3-{[6-(2,4-difluorophenyl)-2-naphthyl]thio}propanenitrile (5.58 g). 1H NMR (500 MHz, CDCl3) δ 7.94 (1H, s), 7.90 (1H, s), 7.85 (2H, d, J=8.5 Hz), 7.66 (1H, d, J=8.3 Hz), 7.50 (2H, d, J=8.6 Hz), 7.00 (1H, dd, J=2.3, 8.6 Hz), 6.96 (1H, d, J=1.9 Hz), 3.24 (2H, t, J=7.2 Hz), 2.64 (2H, t, J=7.3 Hz).
Reaction SMILES: BrCCBr.[Mg].Br[CH:7]1[CH2:10][CH2:9][CH2:8]1.[CH2:11]([O:18][C:19]1[CH:28]=[C:27](I)[CH:26]=[CH:25][C:20]=1[C:21]([O:23][CH3:24])=[O:22])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1>[Cl-].[Zn+2].[Cl-].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Zn].II.C1COCC1.C(OCC)C>[CH2:11]([O:18][C:19]1[CH:28]=[C:27]([CH:7]2[CH2:10][CH2:9][CH2:8]2)[CH:26]=[CH:25][C:20]=1[C:21]([O:23][CH3:24])=[O:22])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: BrC1CCC1
Reactant: COC(=O)c1ccc(I)cc1OCc1ccccc1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: II
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: BrCCBr
Product: COC(=O)c1ccc(C2CCC2)cc1OCc1ccccc1
Reaction time: 1 h
Yield: 59 %

Procedure:
Iodine (40 mg) and 1,2-dibromoethane (0.5 mL) were added to a mixture of magnesium (11.8 g) and anhydrous diethyl ether (250 mL), then bromocyclobutane (44.0 g) was slowly added thereto, and the mixture was stirred at 40C for 2 hours. A THF (450 mL) solution of zinc chloride (54 g) prepared at 160 C under high vacuum was added to the reaction mixture at 0 C, and the mixture was stirred at the same temperature as above for 1 hour. A mixture of methyl 2-(benzyloxy)-4-iodobenzoate (20 g), tris(dibenzylideneacetone)dipalladium(0) (4.97 g), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (3.14 g), and THF (500 mL) was deaerated in an argon stream. The zinc reagent (350 mL) prepared above was added thereto, and the mixture was stirred overnight at 60 C. The reaction mixture was filtered through celite. The solvent was concentrated under reduced pressure. Water was added to the obtained residue, followed by extraction with ethyl acetate three times. Combined organic layers were washed with water and dried over anhydrous sodium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (9.5 g).
Reaction SMILES: C[O:2][CH:3](OC)[C:4]1[CH:9]=[C:8]([O:10][CH3:11])[C:7]([O:12][CH3:13])=[CH:6][C:5]=1Br.C([Li])CCC.[I:22]I.C(O)(=O)C>O1CCCC1>[I:22][C:5]1[CH:6]=[C:7]([O:12][CH3:13])[C:8]([O:10][CH3:11])=[CH:9][C:4]=1[CH:3]=[O:2]
Reactant: COc1cc(Br)c(C(OC)OC)cc1OC
Reactant: II
Agent: [Li]CCCC
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: COc1cc(I)c(C=O)cc1OC
Temperature: -70 °C
Reaction time: 0.5 h
Yield: 72.7 %

Procedure:
2-Bromo-4,5-dimethoxybenzaldehyde dimethylacetal (59 g) is dissolved in tetrahydrofuran and thereto is added 2.5M n-butyllithium (89 ml) under cooling at -70° C. The reaction mixture is kept below -50° C. for 30 minutes and thereto is added dropwise a solution of iodine (51.4 g) in tetrahydrofuran below -50° C. The mixture is kept at the same temperature for 15 minutes and thereto are added aqueous acetic acid to adjust the pH of the solution at 2. The mixture is allowed to stand at room temperature overnight, and the solvent is distilled off from the reaction mixture. The residue is dissolved in ethyl acetate. The solution is washed and dried, and the solvent is distilled off. The residue is crystallized from ethyl acetate to give 2-iodo-4,5-dimethoxybenzaldehyde (43 g). M.p. 139°-141° C.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([NH:12][C:13]([CH3:16])([CH3:15])[CH3:14])(=[O:11])=[O:10])=[CH:5][C:4]=1C.BrC1C=CC(S([Cl:28])(=O)=O)=C(Cl)C=1.CN1C(=O)CCC1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([S:9]([NH:12][C:13]([CH3:16])([CH3:15])[CH3:14])(=[O:11])=[O:10])=[C:5]([Cl:28])[CH:4]=1
Reactant: Cc1cc(S(=O)(=O)NC(C)(C)C)ccc1CN
Reactant: O=S(=O)(Cl)c1ccc(Br)cc1Cl
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: [Al+3]
Solvent: CN1CCCC1=O
Solvent: C1CCOC1
Product: CC(C)(C)NS(=O)(=O)c1ccc(CN)cc1Cl
Temperature: 150 °C
Reaction time: 0.5 h

Procedure:
4-Aminomethyl-N-tert-butyl-2-chloro-benzenesulfonamide was synthesized in a manner analogous to 4-Aminomethyl-N-tert-butyl-3-methyl-benzenesulfonamide in Example 4, using 4-bromo-2-chlorobenzene-1-sulfonyl chloride in place of 4-bromo-3-methylbenzene-1-sulfonyl chloride. In the second step NMP was used as the solvent, Pd(dppf)Cl2 alone was used as catalyst and the reaction mixture was stirred at 150° C. for 30 min, then heated at 120° C. overnight. Reduction of the cyano group to aminomethyl group in the last step was achieved by stirring with lithium aluminium hydride from 0° C. to room temperature in THF.
Reaction SMILES: [C:1]([N:10]([CH2:12][C:13]([NH2:15])=[S:14])[CH3:11])([O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:2].[CH:16]([CH:18](Cl)[C:19]([O:21][CH2:22][CH3:23])=[O:20])=O>ClCCCl>[C:19]([C:18]1[S:14][C:13]([CH2:12][N:10]([C:1]([O:3][C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=2)=[O:2])[CH3:11])=[N:15][CH:16]=1)([O:21][CH2:22][CH3:23])=[O:20]
Reactant: CCOC(=O)C(Cl)C=O
Reactant: CN(CC(N)=S)C(=O)Oc1ccccc1
Solvent: ClCCCl
Product: CCOC(=O)c1cnc(CN(C)C(=O)Oc2ccccc2)s1
Reaction time: 1.5 h

Procedure:
(N-Carbophenoxy-N-methylamino)thioacetamide (46.7 g; 0.21 moles) was combined with ethyl α-formylchloroacetate (30.0 g; 0.20 moles) in 270 ml of 1,2-dichloroethane and heated to reflux temperature for 2 hours. An additional amount of ethyl α-formylchloroacetate (3.0 g; 0.02 moles) was added and heating was continued for 1.5 hours. The reaction mixture was extracted with two 300 ml portions of cold 5% aqueous sodium carbonate, then washed with two 300 ml portions of water and dried over Na2SO4. Evaporation gave the product as an oil which slowly crystallized. Recrystallization from 2-propanol yielded 26 g of the title compound, mp 81°-83°.
Reaction SMILES: [OH-].[K+].C([O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[C:15]3[N:19]([CH:20]=2)[C:18]2[CH:21]=[CH:22][CH:23]=[CH:24][C:17]=2[S:16]3)=[CH:9][CH:8]=1)(=O)C.C(O)(=O)C>CO>[OH:6][C:7]1[CH:8]=[CH:9][C:10]([C:13]2[N:14]=[C:15]3[N:19]([CH:20]=2)[C:18]2[CH:21]=[CH:22][CH:23]=[CH:24][C:17]=2[S:16]3)=[CH:11][CH:12]=1
Reactant: CC(=O)Oc1ccc(-c2cn3c(n2)sc2ccccc23)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: CC(=O)O
Product: Oc1ccc(-c2cn3c(n2)sc2ccccc23)cc1
Reaction time: 1 h
Yield: 86.8 %

Procedure:
In a solution of 2.5 g of potassium hydroxide in 90% methanol was suspended 2 g of 2-(p-acetoxyphenyl)imidazo-[2,1-b]benzothiazole and the suspension was stirred for one hour at 40°-50° C., thereby the additive was completely dissolved. Then, 3 ml of acetic acid was gradually added dropwise to the reaction mixture with stirring, thereby crystals precipitated. The crystals were recovered by filtration, washed with water and then methanol, and dried to provide 1.5 g of 2-(p-hydroxyphenyl)imidazo[2,1-b]benzothiazole.
Reaction SMILES: [CH3:1][N:2]([CH3:11])[C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1.[CH3:12][C:13]1[CH:19]=[C:18]([CH3:20])[CH:17]=[CH:16][C:14]=1[NH2:15]>>[CH3:1][N:2]([CH3:11])[C:3]1[CH:10]=[CH:9][C:6]([CH2:7][NH:15][C:14]2[CH:16]=[CH:17][C:18]([CH3:20])=[CH:19][C:13]=2[CH3:12])=[CH:5][CH:4]=1
Reactant: CN(C)c1ccc(C=O)cc1
Reactant: Cc1ccc(N)c(C)c1
Product: Cc1ccc(NCc2ccc(N(C)C)cc2)c(C)c1
Yield: 95.3 %

Procedure:
By the reaction and treatment in the same manner as in Preparation Example 1 using 4-dimethylaminobenzaldehyde (1.5 g) and 2,4-dimethylaniline (1.2 g) as starting materials, [(4-dimethylaminophenyl)methyl](2,4-dimethylphenyl)amine (2.4 g) was obtained. melting point: 79–80° C.
Reaction SMILES: Cl[Si:2]1(Cl)[CH2:5][CH2:4][CH2:3]1.[C:7]([NH2:11])([CH3:10])([CH3:9])[CH3:8]>>[C:7]([NH:11][Si:2]1([NH:11][C:7]([CH3:10])([CH3:9])[CH3:8])[CH2:5][CH2:4][CH2:3]1)([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(C)N
Reactant: Cl[Si]1(Cl)CCC1
Product: CC(C)(C)N[Si]1(NC(C)(C)C)CCC1
Reaction time: 72 h
Yield: 45 %

Procedure:
Bis(t-butylamino)silacyclobutane (BTBSCB) was synthesized by reacting 1,1-dichlorosilacyclobutane with an excess amount of t-butylamine (Equation 1). To do so, 19.7 ml (0.166 mol) 1,1-dichlorosilacyclobutane was added to 105 ml (0.999 mol) t-butylamine in 1 L hexanes at 0° C. After bodying for three days at the room temperature, the reaction slurry was filtered to remove t-butylamine hydrochloride salt. The filtrant was vacuum dried to give a crude liquid product which was then vacuum distilled. 16 g Product was isolated at 99.2% purity in 45% yield at 71° C. under 50 torr pressure. The structure of the product analyzed with 1H, 13C and 29Si NMR, FT-IR and GC-MS was in consistence with bis(t-butylamino) silacyclobutane.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]([C:17]2[N:18]=[CH:19][N:20](C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH:21]=2)(O)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:6][CH:7]=1.CC(O)C.[OH-].[Na+]>I.C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]([C:17]2[N:18]=[CH:19][NH:20][CH:21]=2)=[CH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: OC(Cc1ccccc1)(c1cccc(Cl)c1)c1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Agent: I
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: ClC(Cl)Cl
Product: Clc1cccc(C(=Cc2ccccc2)c2c[nH]cn2)c1
Temperature: 160 °C

Procedure:
A mixture of 1-(3 Chlorophenyl)-2-phenyl-l-(1-trityl-1H-imidazol-4-yl)ethanol, (Intermediate 15) mg; 0.9 mmol) in 57% aqueous HI (10 mL) and iPrOH (2 mL) was added red phosphorus (280 mg, 9.0 mmol) in a resealable tube was heated at 160° C. for 16 h. The mixture was then cooled to room temperature and poured into ice-water, which was then basified with NaOH and diluted with CHCl3. The residue was isolated in a typical aqueous workup using CHCl3 and purified by MPLC with 5 to 15% MeOH:.CH2Cl2 to give 4-(1-(3-chlorophenyl)-2-phenylvinyl)-1H-imidazole, as a solid, (86 rug), AGN-216677. 1HNMR (CD3OD, 300 MHz) δ 7.71 (s, 1H), 7.37-6.96 (m, 9H), 6.55 (s, 1H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([N:18](C)[C:19](=O)C)[CH:5]=[C:6]([S:8]([C:11]2[CH:16]=[CH:15][C:14]([NH2:17])=[CH:13][CH:12]=2)(=[O:10])=[O:9])[CH:7]=1>O1CCOCC1.[OH-].[Na+]>[NH2:17][C:14]1[CH:15]=[CH:16][C:11]([S:8]([C:6]2[CH:5]=[C:4]([NH:18][CH3:19])[CH:3]=[C:2]([Br:1])[CH:7]=2)(=[O:9])=[O:10])=[CH:12][CH:13]=1
Reactant: CC(=O)N(C)c1cc(Br)cc(S(=O)(=O)c2ccc(N)cc2)c1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CNc1cc(Br)cc(S(=O)(=O)c2ccc(N)cc2)c1
Yield: 54.3 %

Procedure:
0.021 g (0.000054 mol) of N-[3-bromo-5-(4-aminobenzenesulphonyl)-phenyl]-N-methylacetamide was dissolved in a mixture of 10 ml of dioxane and 10 ml of 1N NaOH and heated at reflux for 2 hrs. Subsequently, the organic solvent was distilled off and the residue was made neutral with 1N HCl and extracted with ethyl acetate. The organic phase was washed with water and sat. sodium chloride solution, dried over MgSO4, filtered and concentrated. The residue was chromatographed on silica gel with ethyl acetate/hexane 1:2. There was obtained 0.01 g (54%) of [3-(4-aminobenzenesulphonyl)-5-bromophenyl]-methylamine as yellow crystals. MS (ISP): me/e=343, 341 (C13H14BrN2O2S+).
Reaction SMILES: [N:1]1([CH2:6][C:7]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=2)=[N+:8]([O-:10])[CH3:9])[CH:5]=[CH:4][N:3]=[CH:2]1.[CH3:19][C:20]1[CH:25]=[CH:24][C:23]([S:26][CH2:27][CH:28]=[CH2:29])=[CH:22][CH:21]=1>>[CH3:18][O:17][C:13]1[CH:12]=[C:11]([C:7]2([CH2:6][N:1]3[CH:5]=[CH:4][N:3]=[CH:2]3)[CH2:29][CH:28]([CH2:27][S:26][C:23]3[CH:22]=[CH:21][C:20]([CH3:19])=[CH:25][CH:24]=3)[O:10][N:8]2[CH3:9])[CH:16]=[CH:15][CH:14]=1
Reactant: COc1cccc(C(Cn2ccnc2)=[N+](C)[O-])c1
Reactant: C=CCSc1ccc(C)cc1
Product: COc1cccc(C2(Cn3ccnc3)CC(CSc3ccc(C)cc3)ON2C)c1

Procedure:
The title compound was prepared by a procedure similar to that described in Example 1 by reacting 2-(1H-imidazol-1-yl)-1-(3-methoxyphenyl)-N-methylethanimine N-oxide (1, R1 =3--OCH3) with allyl 4-methyphenyl sulfide (2: R2 =4--CH3). The resulting cis- and trans-diastereomeric mixture of compound 3 (R1 =3--OCH3, R2 =4--CH3, n=0) was flash-chromatographed on neutral silica gel using ethyl acetate as eluent.
Reaction SMILES: [H-].[Na+].[O:3]=[C:4]1[NH:8][CH2:7][CH2:6][N:5]1[CH:9]1[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:11][CH2:10]1.[CH3:25]I>CN(C=O)C>[CH3:25][N:8]1[CH2:7][CH2:6][N:5]([CH:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:16])[CH2:13][CH2:14]2)[C:4]1=[O:3]
Reactant: CI
Reactant: O=C(OCc1ccccc1)N1CCC(N2CCNC2=O)CC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CN1CCN(C2CCN(C(=O)OCc3ccccc3)CC2)C1=O
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Sodium hydride (80 mg) was added to a solution of benzyl 4-(2-oxoimidazolidin-1-yl)piperidin-1-carboxylate (0.30 g) in DMF (5 mL), the mixture was stirred at room temperature for 30 minutes. After addition of methyl iodide (0.25 mL), the mixture was stirred at room temperature for 15 hours. The reaction mixture was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The extract was washed with water, an aqueous 5% citric acid solution and saturated saline solution and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure to obtain the title compound (0.32 g, quantitative) as a colorless oil.