Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1Br.[Li]CCCC.Cl[SiH:15]([CH3:17])[CH3:16]>C1COCC1.CCCCCC>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SiH:15]([CH3:17])[CH3:16]
Reactant: Brc1ccccc1Br
Reactant: C[SiH](C)Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: C[SiH](C)c1ccccc1Br
Reaction time: 0 h
Yield: 68 %

Procedure:
A microsystem composed of three T-shaped micromixers (M1, M2 and M3) and two microtube reactors (R1 and R2) was used. The whole microsystem was dipped in a cooling bath (−78° C.). A solution of o-dibromobenzene (0.27 M) in THF (flow rate: 6 mL/min, 1.62 mmol/min) and a solution of n-BuLi (1.5 M) in n-hexane (flow rate: 1.2 mL/min, 1.8 mmol/min) were introduced to the first T-shaped mixer M1 (inner diameter: 250 μm) by using syringe pumps. The resulting solution was passed through the tube reactor R1 and was mixed with chlorodimethylsilane (HMe2SiCl) (0.65 M) in THF (flow rate: 3 mL/min, 1.95 mmol/min) in the second T-shaped mixer M2 (inner diameter: 500 μm). The solution was introduced to the third T-shaped mixer M3 (inner diameter: 500 μm), where the solution was quenched with methanol (neat, flow rate=3.0 mmol/min). The residence time of the tube reactor R1 (inner diameter: 500 μm, length=50 cm) was 0.82 second. The residence time of the tube reactor R2 (inner diameter: 1,000 μm, length=50 cm) was 2.31 second. After finishing the reaction, an aliquot of the product solution was taken (15 sec) and was analyzed by GC (column, CBP1; 0.25 mm×25 m; initial oven temperature, 50° C.; rate of temperature increase, 10° C./min). As a result, 2-bromophenyldimethylsilane (GC retention time: 14.9 min) was obtained in 68% yield. 1H NMR (400 MHz, CDCl3) δ: 0.40-0.43 (m, 6H), 4.47-4.53 (m, 1H), 7.14-7.27 (m, 2H), 7.42-7.50 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: −3.5, 126.4, 130.6, 130.9, 132.2, 136.4, 139.1. HRMS (EI) m/z: calcd. for C8H11BrSi 213.9813, found 213.9816.
Reaction SMILES: [CH2:1]([C:3]1[CH:7]=[C:6]([CH:8]=[CH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH2:17][CH:18]2[O:20][CH2:19]2)[O:5][N:4]=1)[CH3:2].[C:21]([NH2:25])([CH3:24])([CH3:23])[CH3:22]>>[CH2:1]([C:3]1[CH:7]=[C:6]([CH:8]=[CH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH2:17][CH:18]([OH:20])[CH2:19][NH:25][C:21]([CH3:24])([CH3:23])[CH3:22])[O:5][N:4]=1)[CH3:2]
Reactant: CC(C)(C)N
Reactant: CCc1cc(C=Cc2ccccc2OCC2CO2)on1
Product: CCc1cc(C=Cc2ccccc2OCC(O)CNC(C)(C)C)on1

Procedure:
7 g (0.026 mole) of 3-ethyl-5-[2-(2,3-epoxypropoxy)-styryl]-isoxazole and 3.0 g (0.04 mole) of tert.-butylamine are reacted by the method described for Example 4. 6.6 g (66% of theory), melting point 163°-164° C.
Reaction SMILES: N1C=CN=C1.[CH3:6][C:7]([Si:10](Cl)([CH3:12])[CH3:11])([CH3:9])[CH3:8].[OH:14][CH2:15][CH2:16][C:17]1[O:18][CH:19]=[CH:20][CH:21]=1.CCOCC>CN(C=O)C>[CH3:6][C:7]([Si:10]([CH3:12])([CH3:11])[O:14][CH2:15][CH2:16][C:17]1[O:18][CH:19]=[CH:20][CH:21]=1)([CH3:9])[CH3:8]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCCc1ccco1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCOCC
Product: CC(C)(C)[Si](C)(C)OCCc1ccco1
Temperature: 25 °C
Reaction time: 2 h
Yield: 91.6 %

Procedure:
Imidazole (3.65 g, 53.6 mmol) and TBSCl (6.47 g, 42.9 mmol) were added to the solution of compound 255A (4.00 g, 35.7 mmol) in 50 mL of DMF. The mixture was stirred at rt for 2 h and then the reaction mixture was poured into ether. The ether solution was washed with water (1×), 1 N HCl (1×), water (1×) and brine (1×). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. Purification by flash chromatography on silica gel eluting with 30% CH2Cl2/70% hexane gave 7.4 g (32.7 mmol, 91.7%) of 255B as a colorless oil.
Reaction SMILES: Br[CH2:2][C:3]1[C:12]([C:13](=[O:18])[CH2:14][CH:15]([CH3:17])[CH3:16])=[C:11]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=2)[C:10]2[C:5](=[CH:6][C:7]([O:31][CH3:32])=[C:8]([O:29][CH3:30])[CH:9]=2)[N:4]=1.[CH2:33]([NH:35][CH2:36][CH3:37])[CH3:34]>>[CH2:33]([N:35]([CH2:2][C:3]1[C:12]([C:13](=[O:18])[CH2:14][CH:15]([CH3:17])[CH3:16])=[C:11]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH3:28])[CH:20]=2)[C:10]2[C:5](=[CH:6][C:7]([O:31][CH3:32])=[C:8]([O:29][CH3:30])[CH:9]=2)[N:4]=1)[CH2:36][CH3:37])[CH3:34]
Reactant: COc1ccc(-c2c(C(=O)CC(C)C)c(CBr)nc3cc(OC)c(OC)cc23)cc1OC
Reactant: CCNCC
Product: CCN(CC)Cc1nc2cc(OC)c(OC)cc2c(-c2ccc(OC)c(OC)c2)c1C(=O)CC(C)C

Procedure:
According to the same manner as that described in Example 1, 2-bromomethyl-4-(3,4-dimethoxyphenyl)-3-isovaleryl-6,7-dimethoxyquinoline was reacted with diethylamine to give 2-(N,N-diethylaminomethyl)-4-(3,4-dimethoxyphenyl) -3-isovaleryl-6,7-dimethoxyquinoline. This compound was recrystallized from ethyl acetate-hexane to give colorless prisms. mp. 153°-154° C.
Reaction SMILES: [CH:1]1([N:4]2[C:11](=[O:12])[CH2:10][CH2:9][NH:8][C:7]3[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:6]=3[CH2:5]2)[CH2:3][CH2:2]1.FC(F)(F)S([O-])(=O)=O.[Mg+2].FC(F)(F)S([O-])(=O)=O.[O:36]([CH2:43][CH:44]1[CH2:46][O:45]1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C(=O)(O)[O-].[Na+]>C(#N)C>[CH:1]1([N:4]2[C:11](=[O:12])[CH2:10][CH2:9][N:8]([CH2:46][CH:44]([OH:45])[CH2:43][O:36][C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C:7]3[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:6]=3[CH2:5]2)[CH2:2][CH2:3]1
Reactant: COc1ccc2c(c1)CN(C1CC1)C(=O)CCN2
Reactant: c1ccc(OCC2CO2)cc1
Agent: O=C([O-])O
Agent: O=S(=O)([O-])C(F)(F)F
Agent: [Mg+2]
Solvent: CC#N
Product: COc1ccc2c(c1)CN(C1CC1)C(=O)CCN2CC(O)COc1ccccc1
Temperature: 75 °C
Reaction time: 100 h
Yield: 64.6 %

Procedure:
To a mixture of 5-cyclopropyl-8-methoxy-2,3,5,6-tetrahydrobenzo[b][1,5]diazocin-4(1H)-one (50.0 mg, 0.203 mmol) from Example 1 and magnesium trifluoromethanesulfonate (32.7 mg, 0.102 mmol) in acetonitrile (1.5 ml) was added 2-(phenoxymethyl)oxirane (30.5 mg, 0.203 mmol) and the resulting mixture was stirred at 75° C. for 100 hours. After cooling to room temperature was added sodium bicarbonate (saturated aqueous) and the mixture was extracted with dichloromethane. The organic phases were filtered through a pad of sodium sulfate and the filtrate evaporated. Preparative thin layer chromatography (EtOAc/MeOH: 95/5) of the obtained residue, gave the desired compound as a brown oil (52 mg, 65%).
Reaction SMILES: CC1(C)[O:6][C:5](=[CH:7][C:8](=[O:13])[C:9]([F:12])([F:11])[F:10])[CH2:4][O:3]1>O>[OH:13][C:8]1([C:9]([F:10])([F:11])[F:12])[O:3][CH2:4][C:5](=[O:6])[CH2:7]1
Reactant: CC1(C)OCC(=CC(=O)C(F)(F)F)O1
Solvent: O
Product: O=C1COC(O)(C(F)(F)F)C1
Temperature: 20 °C
Reaction time: 24 h

Procedure:
A mixture of 3-(2,2-dimethyl-1,3-dioxolan-4-ylidene)-1,1,1-trifluoroacetone (5.21 g, 24.8 mmol) and 20 ml water was stirred at 20° C. for 24 hours. The volatile components were removed under a reduced pressure of 20 mbar. The product was extracted with dichloromethane and the organic phase was dried over MgSO4 and concentrated. The precipitate was purified by crystallization from toluene.
Reaction SMILES: [H-].[Na+].[O:3]=[C:4]1[C:8]2=[C:9]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[NH:10][C:11](=[O:12])[C:7]2=[C:6]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[NH:5]1.Cl[C:26]([O:28][CH2:29][CH2:30][CH2:31][CH3:32])=[O:27]>O1CCCC1>[CH2:29]([O:28][C:26]([N:10]1[C:9]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:8]2[C:7](=[C:6]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:5]([C:26]([O:28][CH2:29][CH2:30][CH2:31][CH3:32])=[O:27])[C:4]2=[O:3])[C:11]1=[O:12])=[O:27])[CH2:30][CH2:31][CH3:32]
Reactant: CCCCOC(=O)Cl
Reactant: O=C1NC(c2ccccc2)=C2C(=O)NC(c3ccccc3)=C12
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCOC(=O)N1C(=O)C2=C(c3ccccc3)N(C(=O)OCCCC)C(=O)C2=C1c1ccccc1
Reaction time: 24 h

Procedure:
0.28 g (0.007 mol) of solid sodium hydride is added to a suspension of 0.5 g (0.00175 mol) of 1,4-diketo-2,5-dihydro-3,6-diphenyl-pyrrolo[3,4-c]pyrrole in 17 ml of tetrahydrofuran in an argon atmosphere. After the resulting mixture is stirred for 24 hours, 0.67 ml (0.007 mol) of n-butyl chloroformate is added thereto, and the resulting suspension is stirred overnight. The mixture is filtered, and the filtrate is concentrated under reduced pressure. The residue is taken into water/diethyl ether, and the organic phase is dried over MgSO4 and then concentrated under reduced pressure. The residue is taken into n-hexane, and the yellow powder precipitated is collected by filtration, washed with a small amount of n-hexane to give 0.62 g (73% of the theoretical value) of N,N'-bis(n-butoxycarbonyl)-1,4-diketo-2,5-dihydro-3,6-diphenyl-pyrrolo[3,4-c]pyrrole as a yellow fluorescent powder.
Reaction SMILES: [CH2:1]([S:3](Cl)(=[O:5])=[O:4])[CH3:2].Cl.[Br:8][C:9]1[CH:10]=[C:11]2[C:15](=[C:16]([C:18]([NH2:20])=[O:19])[CH:17]=1)[NH:14][CH:13]=[C:12]2[CH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.C(N(CC)CC)C.CCOC(C)=O.O>CN(C=O)C>[Br:8][C:9]1[CH:10]=[C:11]2[C:15](=[C:16]([C:18]([NH2:20])=[O:19])[CH:17]=1)[NH:14][CH:13]=[C:12]2[CH:21]1[CH2:26][CH2:25][N:24]([S:3]([CH2:1][CH3:2])(=[O:5])=[O:4])[CH2:23][CH2:22]1
Reactant: NC(=O)c1cc(Br)cc2c(C3CCNCC3)c[nH]c12
Reactant: CCS(=O)(=O)Cl
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: O
Product: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(Br)cc23)CC1
Temperature: 0 °C
Reaction time: 0.75 h
Yield: 83.4 %

Procedure:
Ethanesulfonyl chloride (4.5 mL, 47.4 mmol) was added dropwise to a solution of 5-bromo-3-(4-piperidinyl)-1H-indole-7-carboxamide hydrochloride (8.49 g, 23.7 mmol) and triethylamine (13.2 mL, 94.7 mmol) in DMF (80 mL) at 0° C. (bath temperature). The reaction mixture was stirred at 0° C. for 45 min. and was then poured into a 2:1 mixture of EtOAc/H2O (300 mL). The resulting precipitate was filtered off, washed with EtOAc (2×50 mL), and set aside. The EtOAc/H2O bilayer was separated, and the aqueous layer was extracted with EtOAc (2×100 mL). The combined organic layers were washed with saturated NaCl (1×100 mL), dried (MgSO4), filtered, and concentrated under reduced pressure. The crude product was combined with the precipitate isolated above and washed with MeOH (1×10 mL) to give 8.19 g of the title compound (83%).
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][CH2:6][C:7]([NH:9][C:10]1[C:15]([CH3:16])=[CH:14][CH:13]=[C:12]([N+:17]([O-:19])=[O:18])[C:11]=1[CH3:20])=[O:8])[CH3:4].Br[CH:22]([CH3:27])[C:23]([O:25][CH3:26])=[O:24].O>O1CCCC1>[CH3:26][O:25][C:23]([CH:22]([N:9]([C:7](=[O:8])[CH2:6][O:5][CH2:3][CH3:4])[C:10]1[C:15]([CH3:16])=[CH:14][CH:13]=[C:12]([N+:17]([O-:19])=[O:18])[C:11]=1[CH3:20])[CH3:27])=[O:24]
Reactant: CCOCC(=O)Nc1c(C)ccc([N+](=O)[O-])c1C
Reactant: COC(=O)C(C)Br
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCOCC(=O)N(c1c(C)ccc([N+](=O)[O-])c1C)C(C)C(=O)OC
Temperature: 55 °C

Procedure:
To a solution of 3 g of 55% sodium hydride in 70 ml of anhydrous tetrahydrofurane saturated with nitrogen is added dropwise, at room temperature, with stirring and while simultaneously introducing nitrogen, a solution of 16 g N-ethoxyacetyl-2,6-dimethyl-3-nitroaniline in 30 ml of the same solvent. After the weakly exothermic reaction has subsided, the mixture is heated to 55° C. and 12.7 g of methyl 2-bromopropionate in 20 ml of tetrahydrofurane are added. During this addition the temperature rises to 60° C. The mixture is stirred for 12 hours at 55° C., then cooled to room temperature, poured into 100 ml of water and extracted with two 100 ml portions of ethyl acetate. The combined extracts are washed with water, dried over sodium sulfate, and excess solvent is removed in vacuo. The oily crude product is purified by column chromatography over silica gel, using a 1:1 mixture of chloroform/diethyl ether as eluant. Fractions 5 to 30 are combined and the eluant is removed in vacuo. Compound 31 is a viscous oil with a refractive index of nD24 =1.5325.
Reaction SMILES: [NH2:1][C:2]1[S:3][C:4]2[C:10]([N+:11]([O-:13])=[O:12])=[C:9]([O:14][C:15]3[CH:16]=[C:17]([NH:21][C:22](=[O:34])[C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([C:32]#[N:33])([CH3:31])[CH3:30])[CH:24]=4)[CH:18]=[CH:19][CH:20]=3)[CH:8]=[CH:7][C:5]=2[N:6]=1.[CH:35]1([C:38](Cl)=[O:39])[CH2:37][CH2:36]1>N1C=CC=CC=1>[C:32]([C:29]([C:25]1[CH:24]=[C:23]([CH:28]=[CH:27][CH:26]=1)[C:22]([NH:21][C:17]1[CH:18]=[CH:19][CH:20]=[C:15]([O:14][C:9]2[CH:8]=[CH:7][C:5]3[N:6]=[C:2]([NH:1][C:38]([CH:35]4[CH2:37][CH2:36]4)=[O:39])[S:3][C:4]=3[C:10]=2[N+:11]([O-:13])=[O:12])[CH:16]=1)=[O:34])([CH3:30])[CH3:31])#[N:33]
Reactant: CC(C)(C#N)c1cccc(C(=O)Nc2cccc(Oc3ccc4nc(N)sc4c3[N+](=O)[O-])c2)c1
Reactant: O=C(Cl)C1CC1
Solvent: c1ccncc1
Product: CC(C)(C#N)c1cccc(C(=O)Nc2cccc(Oc3ccc4nc(NC(=O)C5CC5)sc4c3[N+](=O)[O-])c2)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 79.1 %

Procedure:
To a solution of N-{3-[(2-amino-7-nitro-1,3-benzothiazol-6-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide (3.0 g, 6.33 mmol) in pyridine (30 mL) was added cyclopropanecarbonyl chloride (1.15 ml, 12.7 mmol) at 4° C., and the mixture was stirred at room temperature for 4 hr. The reaction mixture was concentrated under reduced pressure. The obtained residue was diluted with ethyl acetate (300 mL)/tetrahydrofuran (30 mL), washed successively with 5% aqueous sodium hydrogen carbonate solution (200 mL) and saturated brine (200 mL), and dried over anhydrous sodium sulfate. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (ethyl acetate/n-hexane=30/70→100/0), and the obtained solution was concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/n-hexane to give the title compound (2.71 g, 79%) as a yellow powder.
Reaction SMILES: [F:1][C:2]([F:8])([F:7])[S:3]([OH:6])(=[O:5])=[O:4].[N:9]1[CH:14]=[CH:13][C:12]([CH2:15][S:16]([OH:19])(=O)=[O:17])=[CH:11][CH:10]=1.N1C=CC=CC=1CS(O)(=O)=O.P(Cl)(Cl)(Cl)(Cl)[Cl:32]>P(Cl)(Cl)(Cl)=O>[OH:6][S:3]([C:2]([F:8])([F:7])[F:1])(=[O:5])=[O:4].[N:9]1[CH:14]=[CH:13][C:12]([CH2:15][S:16]([Cl:32])(=[O:19])=[O:17])=[CH:11][CH:10]=1
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: O=S(=O)(O)Cc1ccncc1
Agent: O=S(=O)(O)C(F)(F)F
Agent: O=S(=O)(O)Cc1ccccn1
Solvent: O=P(Cl)(Cl)Cl
Product: O=S(=O)(Cl)Cc1ccncc1
Temperature: 25 °C
Yield: 82.9 %

Procedure:
Trifluoromethanesulfonic acid (100 g, 0.67 mol) was rapidly added to a suspension of 4-pyridylmethanesulfonic acid (103 g, 0.6 mol) in phosphorous oxychloride (300 ml). The pyridylmethanesulfonic acid dissolved and reprecipitated as the triflate salt. The resulting suspension was cooled in ice for 30 min, then treated with phosphorous pentachloride (139 g, 0.67 mol) in Portions during 10 minutes. The mixture was allowed to warm to room temperature over 30 min and was then cautiously heated to reflux over a period of 1.5 hrs during which time extensive gas evolution occurred. After refluxing for 1 hr, the excess phosphorous oxychloride was distilled off under vacuum while maintaining the pot temperature below 80° C. The residual solid was dissolved in acetonitrile (200 ml), filtered and crystallized by the gradual addition of ether (400 ml). The product was recovered by filtration and washed with ether to afford a white solid (170 g, 84%).
Reaction SMILES: [CH2:1]([C:3]1([CH3:20])[C:7](=[O:8])[C:6](I)=[C:5]([C:10]2[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=2)[O:4]1)[CH3:2].C(=O)([O-])[O-].[Na+].[Na+].[C:27]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)(=[O:29])[CH3:28]>C1(C)C=CC=CC=1.C(O)C.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>[C:27]([C:30]1[CH:35]=[CH:34][C:33]([C:6]2[C:7](=[O:8])[C:3]([CH2:1][CH3:2])([CH3:20])[O:4][C:5]=2[C:10]2[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=2)=[CH:32][CH:31]=1)(=[O:29])[CH3:28]
Reactant: CC(=O)c1ccc(B(O)O)cc1
Reactant: CCC1(C)OC(c2ccc(S(C)(=O)=O)cc2)=C(I)C1=O
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: CCO
Solvent: Cc1ccccc1
Product: CCC1(C)OC(c2ccc(S(C)(=O)=O)cc2)=C(c2ccc(C(C)=O)cc2)C1=O
Temperature: 95 °C
Reaction time: 12 h
Yield: 61.2 %

Procedure:
To a stirred solution of 2-ethyl-4-iodo-2-methy-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone (200 mg) in 15 ml toluene and 5 ml ethanol, were added 34 mg of tetrakis(triphenylphosphine)palladium(0), 5 ml of 2M aqueous sodium carbonate solution and 120 mg of 4-acetylbenzeneboronic acid. Then the reaction solution was stirred at 95° C. for 12 hours. The reaction solvent was evaporated off under reduced pressure and the resulting residue was extracted with 50 ml water and dichloromethane (30 ml×3). Then the organic layer was concentrated in vacuo and the resulting crude product was purified by column chromatography (hexane/ethylacetate) to afford 120 mg of 4-(4-acetylphenyl)-2-ethyl-2-methyl-5-{4-(methylsulfonyl)phenyl}-3(2H)-furanone as a solid. mp: 147-148° C. NMR: δ0.97 (t, J=7.5 Hz, 3H), 1.56 (s, 3H), 1.99 (m, 2H), 2.62 (s, 3H), 3.08 (s, 3H), 7.39 (d, J=8.7 Hz, 2H), 7.83 (d, J=8.7 Hz, 2H), 7.97 (m, 2H). IR (cm−1): 2929, 1684, 1410, 1317, 1149, 1016, 769, 552.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([F:12])[C:5]([O:10][CH3:11])=[C:6]([CH:9]=1)[CH2:7][OH:8].N1C=CN=C1.Cl[Si:19]([C:32]([CH3:35])([CH3:34])[CH3:33])([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CN(C)C=O.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]([F:12])[C:5]([O:10][CH3:11])=[C:6]([CH:9]=1)[CH2:7][O:8][Si:19]([C:32]([CH3:35])([CH3:34])[CH3:33])([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: COc1c(F)cc(Br)cc1CO
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COc1c(F)cc(Br)cc1CO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 50 °C
Reaction time: 0.5 h
Yield: 103.1 %

Procedure:
907 mg of 5-bromo-3-fluoro-2-methoxybenzyl alcohol was dissolved in 10 ml of N,N-dimethylformamide. 400 mg of imidazole and 1.06 g of chloro(t-butyl)diphenylsilane were added, followed by stirring for 1 hour at room temperature and for 0.5 hours at 50° C. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated, to give 1.882 g of [(5-bromo-3-fluoro-2methoxybenzyl)oxy](t-butyl)diphenylsilane.
Reaction SMILES: [F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([NH:13][C:14](=[O:27])[C:15]2[CH:20]=[C:19]([S:21](=[O:24])(=[O:23])[NH2:22])[CH:18]=[CH:17][C:16]=2[O:25][CH3:26])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.CO[CH:32]1[CH2:36][CH2:35][CH:34](OC)O1.C(O)(=O)C>O>[F:29][C:2]([F:1])([F:28])[C:3]1[CH:4]=[C:5]([NH:13][C:14](=[O:27])[C:15]2[CH:20]=[C:19]([S:21]([N:22]3[CH:32]=[CH:36][CH:35]=[CH:34]3)(=[O:23])=[O:24])[CH:18]=[CH:17][C:16]=2[O:25][CH3:26])[CH:6]=[C:7]([C:9]([F:12])([F:10])[F:11])[CH:8]=1
Reactant: COC1CCC(OC)O1
Reactant: COc1ccc(S(N)(=O)=O)cc1C(=O)Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Solvent: O
Solvent: CC(=O)O
Product: COc1ccc(S(=O)(=O)n2cccc2)cc1C(=O)Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Yield: 88.6 %

Procedure:
A mixture of N-[3,5-bis(trifluoromethyl)phenyl]-2-methoxy-5-sulfamoyl-benzamide (compound of Example 87(2); 442 mg, 1 mmol), 2,5-dimethoxytetrahydrofuran (159 mg, 1.2 mmol) and acetic acid (5 mL) was refluxed for 2 hours. After cooling, the reaction mixture was poured into water and extracted with ethyl acetate. After the organic layer was washed with water, saturated aqueous sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate, the residue obtained by evaporation of the solvent under reduced pressure was purified by chromatography on silica gel (n-hexane:ethyl acetate=3:2) to give the title compound (436.5 mg, 88.6%) as a white solid.
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].[CH2:5]([O:12][C:13]1[CH:14]=[CH:15][C:16]([C@@H:24]([O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])[CH2:25]Br)=[C:17]2[C:22]=1[NH:21][C:20](=[O:23])[CH:19]=[CH:18]2)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.O>CN(C=O)C>[N:1]([CH2:25][C@@H:24]([C:16]1[CH:15]=[CH:14][C:13]([O:12][CH2:5][C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=2)=[C:22]2[C:17]=1[CH:18]=[CH:19][C:20](=[O:23])[NH:21]2)[O:27][Si:28]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:30])[CH3:29])=[N+:2]=[N-:3]
Reactant: [N-]=[N+]=[N-]
Reactant: CC(C)(C)[Si](C)(C)O[C@@H](CBr)c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)O[C@@H](CN=[N+]=[N-])c1ccc(OCc2ccccc2)c2[nH]c(=O)ccc12
Temperature: 80 °C
Yield: 148.3 %

Procedure:
NaN3 (266 mg, 4.1 mmol) was added to a stirring solution of (R)-8-(benzyloxy)-5-[2-bromo-1-[(tert-butyldimethylsilyl)oxy]ethyl]quinolin-2(1H)-one (1 g, 2.05 mmol) in DMF (20 mL) at rt and warmed to 80° C. for 3 h. The resulting solution was poured into H2O (80 mL) and extracted with EtOAc (3×50 mL). The combined organic layers were washed with H2O (2×100 mL), brine (100 mL), dried over Na2SO4 (s), and concentrated to give the title compound (1.37 g) as yellow solid. The compound was used with no further purification. ES/MS calcd. for C24H31N4O3Si+ 451.2. Found m/z=451.3 (M+H)+.
Reaction SMILES: [CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]([O:12]C)=[O:11])[CH2:5][CH2:4]1)[CH3:2]>Cl>[CH2:1]([N:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]([OH:12])=[O:11])[CH2:5][CH2:4]1)[CH3:2]
Reactant: CCN1CCN(CC(=O)OC)CC1
Agent: Cl
Product: CCN1CCN(CC(=O)O)CC1
Yield: 54.5 %

Procedure:
The solution of methyl 2-(4-ethylpiperazin-1-yl)acetate (1.3 g, 6.50 mmol, 1.0 eq) in 8 N HCl was stirred at 95° C. for 16 h and concentrated on vacuum pump. The mixture was quenched with sodium bicarbonate solution and extracted with ethyl acetate (3×150 ml). The combined organic layer was washed with water, brine and dried over sodium sulphate. The solvent was distilled off to give the product in 54.5% yield (0.6 g). LC-MS (ESI): Calculated mass: 158.0; Observed mass: 159.1 [M+H]+ (rt: 0.102 min).
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:12][CH2:13][CH3:14])[CH2:5][O:6][CH2:7][CH2:8][CH2:9][CH2:10][OH:11])[CH3:2].[Cl:15][C:16]1[CH:21]=[C:20]([O:22][CH2:23][CH:24]=[C:25]([Cl:27])[Cl:26])[CH:19]=[C:18]([Cl:28])[C:17]=1O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1>[Cl:15][C:16]1[CH:21]=[C:20]([O:22][CH2:23][CH:24]=[C:25]([Cl:27])[Cl:26])[CH:19]=[C:18]([Cl:28])[C:17]=1[O:11][CH2:10][CH2:9][CH2:8][CH2:7][O:6][CH2:5][CH:4]([O:3][CH2:1][CH3:2])[O:12][CH2:13][CH3:14]
Reactant: CCOC(COCCCCO)OCC
Reactant: Oc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCOC(COCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl)OCC
Yield: 92.1 %

Procedure:
To a mixture of 2.30 g of 4-(2,2-diethoxyethoxy)butanol, 2.94 g of 2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenol, 2.94 g of triphenylphosphine, and 30 ml of tetrahydrofuran was slowly added dropwise 2.48 g of diisopropylazodicarboxylate with stirring in a stream of nitrogen gas under ice cooling. After stirring at room temperature for 24 hours, the reaction mixture was concentrated to give a residue. This residue was subjected to silica gel chromatography, which afforded 4.48 g (yield, 73%) of 3,5-dichloro-1-(3,3-dichloro-2-propenyloxy)-4-(4-(2,2-diethoxyethoxy)butyloxy)benzene.