Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20](Cl)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1>>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]2[O:23][C:17]3=[CH:18][N:19]=[C:20]([C:27]4[CH:28]=[CH:29][N:24]=[CH:25][CH:26]=4)[CH:21]=[C:16]3[CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCC(C2Cc3cc(Cl)ncc3O2)CC1
Reactant: OB(O)c1ccncc1
Product: CC(C)(C)OC(=O)N1CCC(C2Cc3cc(-c4ccncc4)ncc3O2)CC1

Procedure:
The title compound is prepared from 4-(5-chloro-2,3-dihydro-furo[2,3-c]pyridin-2-yl)-piperidine-1-carboxylic acid tert-butyl ester and pyridine-4-boronic acid following a procedure analogous to that described in Example 28. LC (method 10): tR=1.50 min; Mass spectrum (ESI+): m/z=382 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([NH:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:3]=1.[C:16]([O:19][CH2:20][C:21]1[CH:25]=[CH:24][O:23][C:22]=1[C:26](=[O:29])[CH2:27]Br)(=[O:18])[CH3:17]>>[C:16]([O:19][CH2:20][C:21]1[CH:25]=[CH:24][O:23][C:22]=1[C:26]([C:27]1[N:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:4]2[C:5]([C:6]=1[NH2:7])=[CH:8][CH:9]=[C:2]([Cl:1])[CH:3]=2)=[O:29])(=[O:18])[CH3:17]
Reactant: CCOC(=O)Nc1cc(Cl)ccc1C#N
Reactant: CC(=O)OCc1ccoc1C(=O)CBr
Product: CCOC(=O)n1c(C(=O)c2occc2COC(C)=O)c(N)c2ccc(Cl)cc21

Procedure:
The title compound was prepared according to the procedure described in step 2 of Example 1 from 4-chloro-2-[(ethoxycarbonyl)amino]benzonitrile (Example 1, step 1) and 3-acetoxymethyl-2-(bromoacetyl)furan (Step 1).
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([O:17][C:18]2[CH:23]=[CH:22][C:21]([NH2:24])=[C:20]([CH2:25][S:26]([C:29]3[C:38]4[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH:32]=[CH:31][CH:30]=3)(=[O:28])=[O:27])[CH:19]=2)[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:39]([O-])=O.[Na+].C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.Cl.O>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([O:17][C:18]2[CH:19]=[C:20]3[C:21](=[CH:22][CH:23]=2)[NH:24][N:39]=[C:25]3[S:26]([C:29]2[C:38]3[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH:32]=[CH:31][CH:30]=2)(=[O:28])=[O:27])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Nc1ccc(OC2CCN(C(=O)OCc3ccccc3)CC2)cc1CS(=O)(=O)c1cccc2ccccc12
Reactant: O=N[O-]
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: O=C(OCc1ccccc1)N1CCC(Oc2ccc3[nH]nc(S(=O)(=O)c4cccc5ccccc45)c3c2)CC1
Reaction time: 1 h
Yield: 55.9 %

Procedure:
A suspension of 4-[4-amino-3-(1-naphthylsulfonylmethyl)phenoxy]piperidin-1-ylcarboxylic acid benzyl ester (3.2 g, 6.0 mmol) in ethanol and 1.0 N HCl (155 mL) was heated to aid dissolution, treated slowly with sodium nitrite (0.67 g, 9.7 mmol) in water, stirred at ambient temperatures for one hour, basified with solid sodium carbonate, stirred at ambient temperature for 1 hour and concentrated in vacuo. The resultant residue was partitioned in ethyl acetate and brine. The phases were separated; the organic phase was dried over anhydrous magnesium sulfate and concentrated in vacuo. This residue was purified by flash chromatography with 35-40% ethyl acetate in hexane and 100% ethyl acetate to give 4-[3-(1-naphthylsulfonyl)-1H-indazol-5-yloxy]piperidin-1-ylcarboxylic acid benzyl ester as a light orange foam, 1.79 g (55.9% yield), Mass spectrum (+EI, [M+H]+) m/z 542. 1HNMR (500 MHz, DMSO-d6): δ14.07 (s, 1H), 8.71-8.73 (m, 1H), 8.55 (dd, 1H, J=7.45 Hz and 1.22 Hz), 8.26 (d, 1H, J=8.29 Hz), 8.01-8.03 (m, 1H), 7.70-7.74 (m, 1H), 7.51-7.62 (m, 3H), 7.27-7.35 (m, 5H), 7.23 (d, 1H, J=2.20 Hz), 7.09 (dd, 1H, J=9.03 Hz and 2.32 Hz), 5.06 (s, 2H), 4.59-4.61 (m, 1H), 3.63-3.72 (m, 2H), 3.29-3.33 (m, 2H), 1.83-1.88 (m, 2H), 1.50-1.55 ppm (m, 2H
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][NH:7][CH2:8][C:9]1[CH:33]=[CH:32][C:12]([CH2:13][N:14]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:15][CH2:16][CH2:17][CH2:18][N:19]([CH2:23][CH2:24][CH3:25])[CH2:20][CH2:21][CH3:22])=[CH:11][CH:10]=1.[CH3:34][N:35]1[CH:39]=[CH:38][N:37]=[C:36]1[CH:40]=O.C([BH3-])#N.[Na+].C(O)(=O)C>CO>[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][N:7]([CH2:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][N:14]([C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:15][CH2:16][CH2:17][CH2:18][N:19]([CH2:20][CH2:21][CH3:22])[CH2:23][CH2:24][CH3:25])=[CH:32][CH:33]=1)[CH2:40][C:36]1[N:35]([CH3:34])[CH:39]=[CH:38][N:37]=1
Reactant: CCCN(CCC)CCCCN(Cc1ccc(CNCc2ncc[nH]2)cc1)c1ccccc1
Reactant: Cn1ccnc1C=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CCCN(CCC)CCCCN(Cc1ccc(CN(Cc2ncc[nH]2)Cc2nccn2C)cc1)c1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 59.4 %

Procedure:
The compound (45.5 mg) obtained in Example 24-3 was dissolved in anhydrous methanol (1.8 ml) and added with 1-methyl-2-imidazole carboxaldehyde (16.5 mg) and sodium cyanoborohydride (18.9 mg). The solution was adjusted to pH 5 with acetic acid and stirred at room temperature for 24 hours. After completion of the reaction, the solvent was distilled off and the resultant was added with a 1 mol/l sodium hydroxide aqueous solution and subjected to extraction with chloroform. The resultant was dried with magnesium sulfate and the solvent was distilled off. The residue was purified through silica gel column chromatography (chloroform/ethyl acetate) and treated with hydrochloric acid, thereby obtaining a hydrochloride (32.7 mg) of the subject compound as a white solid.
Reaction SMILES: [CH2:1]([OH:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].N1C2C(=CC=CC=2)C=CC=1.[Cl-].[CH2:31]([O:33][C:34](=[O:40])/[CH:35]=[CH:36]/[C:37](O)=[O:38])[CH3:32]>C(O)C>[C:34]([O:33][CH2:31][CH3:32])(=[O:40])/[CH:35]=[CH:36]/[C:37]([O:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[O:38]
Reactant: CCOC(=O)/C=C/C(=O)O
Reactant: CCCCCCCCCCCCCCCCCCO
Agent: [Cl-]
Solvent: c1ccc2ncccc2c1
Solvent: CCO
Product: CCCCCCCCCCCCCCCCCCOC(=O)/C=C/C(=O)OCC
Reaction time: 2 h

Procedure:
135 g (0.5 mole) of 1-octadecanol and 65 ml (0.55 mole) of quinoline are dissolved, with stirring, at 40° C. in 500ml of ethanol-free chloroform. Over the course of one hour, 89.4 g (0.55 mole) of fumaric acid monoethylesterchloride were added drop by drop to the clear solution and it was boiled for 2 hours under reflux. The reaction mixture was diluted with 500 ml of petroleum ether and extracted twice with 0.5N hydrochloric acid, water, 5% potassium carbonate solution and water, dried over sodium sulfate and concentrated under reduced pressure. The solid residue was recrystallized from 95% ethanol. Yield: 139 g of product having a melting point of 42° C.
Reaction SMILES: CCCCCC.C([Li])CCC.Br[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[F:20].[F:21][C:22]([F:30])([S:28][CH3:29])[C:23](OCC)=[O:24].Cl>CCOCC>[F:20][C:14]1[CH:15]=[C:16]([F:19])[CH:17]=[CH:18][C:13]=1[C:23](=[O:24])[C:22]([F:30])([F:21])[S:28][CH3:29]
Reactant: CCOC(=O)C(F)(F)SC
Reactant: Fc1ccc(Br)c(F)c1
Agent: Cl
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: CCCCCC
Product: CSC(F)(F)C(=O)c1ccc(F)cc1F
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 79.7 %

Procedure:
A hexane solution (13.7 ml, 21.6 mmol) of 1.58 M n-butyllithium was added dropwise to a solution of 1-bromo-2,4-difluorobenzene (4.2 g, 21.8 mmol) in absolute ether (60 ml) at −70° C., and the mixture was stirred for 15 minutes at the same temperature. A solution of ethyl 2,2-difluoro-2-(methylthio)acetate (3.7 g, 21.6 mmol) in absolute ether (20 ml) was added to this solution at −70° C. After the resultant mixture was stirred for 1 hour at the same temperature, the temperature of the reaction mixture was raised to 0° C. for 1 hour. The reaction mixture was poured into diluted hydrochloric acid-containing ice to conduct extraction with ether. After the resultant ether solution was washed with water and dried, the solvent was distilled off. The resultant residue was purified by distillation under reduced pressure to obtain 1-(2,4-difluorophenyl)-2,2-difluoro-2-(methylthio)-1-ethanone (4.1 g, yield: 90.0%) as a colorless oil.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([CH3:11])=[O:10])=[CH:4][CH:3]=1.N1C=CC=CC=1.Cl[C:19]([O:21][CH2:22][C:23]([Cl:26])([Cl:25])[Cl:24])=[O:20]>O1CCCC1>[O:10]=[C:9]([CH3:11])[CH2:8][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:19](=[O:20])[O:21][CH2:22][C:23]([Cl:26])([Cl:25])[Cl:24])=[CH:7][CH:6]=1
Reactant: CC(=O)Cc1ccc(N)cc1
Reactant: O=C(Cl)OCC(Cl)(Cl)Cl
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: CC(=O)Cc1ccc(NC(=O)OCC(Cl)(Cl)Cl)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 58.6 %

Procedure:
To a solution of 1-(4-aminophenyl)acetone (1.13 g, 7.57 mmol) and pyridine (1.84 ml, 22.7 mmol) in tetrahydrofuran (50 ml) was added 2,2,2-trichloroethyl chloroformate (1.57 ml, 11.4 mmol) with ice-cooling, and the mixture was stirred for 1 hour with ice-cooling and then at room temperature for 1 hour, the reaction mixture was poured into ice-water and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate=1:1) to obtain the desired product (1.44 g, 58.4%) as an oil.
Reaction SMILES: Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]2[CH2:21][CH2:20][C:19]3[C:14](=[CH:15][C:16]([C:22]4[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=4)=[CH:17][CH:18]=3)[CH:13]=2)=[O:11])=[CH:5][CH:4]=1.[CH3:29][O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[CH3:29][O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[N:37]1[CH2:42][CH2:41][N:40]([CH2:2][C:3]2[CH:8]=[CH:7][C:6]([NH:9][C:10]([C:12]3[CH2:21][CH2:20][C:19]4[C:14](=[CH:15][C:16]([C:22]5[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=5)=[CH:17][CH:18]=4)[CH:13]=3)=[O:11])=[CH:5][CH:4]=2)[CH2:39][CH2:38]1
Reactant: Cc1ccc(-c2ccc3c(c2)C=C(C(=O)Nc2ccc(CCl)cc2)CC3)cc1
Reactant: COc1ccccc1N1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccccc1N1CCN(Cc2ccc(NC(=O)C3=Cc4cc(-c5ccc(C)cc5)ccc4CC3)cc2)CC1
Temperature: 25 °C
Reaction time: 13 h
Yield: 67.5 %

Procedure:
In DMF (3 ml) was dissolved N-[4-(chloromethyl)phenyl]-7-(4-methylphenyl)-3,4-dihydronaphthalene-2-carboxamide (150 mg), and to the solution were added 1-(2-methoxyphenyl)piperazine (97 mg) and potassium carbonate (268 mg). The mixture was stirred at room temperature for 13 hours, and to the mixture was added water (50 ml). The mixture was extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-diisopropylether to give N-[4-[1-(2-methoxyphenyl)-4-piperazinylmethyl]phenyl]-7-(4-methylphenyl)-3,4-dihydronaphthalene-2-carboxamide (Compound 41) (142 mg) as colorless crystals.
Reaction SMILES: [CH3:1][C:2]1([C:7]2[CH:14]=[CH:13][C:10]([CH2:11][OH:12])=[CH:9][CH:8]=2)[O:6][CH2:5][CH2:4][O:3]1.Br[C:16]1[S:17][C:18]([Br:21])=[CH:19][N:20]=1>>[CH2:4]1[O:3][C:2]([C:7]2[CH:14]=[CH:13][C:10]([CH2:11][O:12][C:16]3[S:17][C:18]([Br:21])=[CH:19][N:20]=3)=[CH:9][CH:8]=2)([CH3:1])[O:6][CH2:5]1
Reactant: Brc1cnc(Br)s1
Reactant: CC1(c2ccc(CO)cc2)OCCO1
Product: CC1(c2ccc(COc3ncc(Br)s3)cc2)OCCO1
Yield: 60 %

Procedure:
Using an analogous procedure to that described in the first paragraph of the portion of Example 43 which is concerned with the preparation of starting materials, 4-(2-methyl-1,3-dioxolan-2-yl)benzyl alcohol was reacted with 2,5-dibromothiazole to give 4'-(5-bromothiazole-2-yloxymethyl)acetophenone ethylene acetal in 60% yield as an oil.
Reaction SMILES: [CH2:1]([Mg]Cl)[CH2:2][CH3:3].C(OCC)C.[Br:11][C:12]1[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:13]=1[CH:14]=[O:15].[Cl-].[NH4+]>O1CCCC1.[Cl-].[Zn+2].[Cl-]>[Br:11][C:12]1[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:13]=1[CH:14]([OH:15])[CH2:1][CH2:2][CH3:3]
Reactant: O=Cc1cccc(Cl)c1Br
Reactant: CCC[Mg]Cl
Agent: [Cl-]
Agent: [NH4+]
Agent: [Zn+2]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCCC(O)c1cccc(Cl)c1Br
Temperature: 25 °C
Yield: 62 %

Procedure:
Under an argon atmosphere, zinc chloride (0.68 g, 4.97 mmol) was added to a 2.0 M solution of n-propyl magnesium chloride in diethyl ether (12.42 mL, 24.93 mmol), and the mixture was stirred at room temperature. After stirring for 0.5 hours, a solution of 2-bromo-3-chlorobenzaldehyde (4.36 g, 19.87 mmol), which had been obtained in Reference example 5(5b), in tetrahydrofuran (10 mL) was added dropwise thereto. After stirring for 2 hours under ice cooling, a saturated aqueous ammonium chloride solution (20 mL) was added thereto. The mixture obtained was extracted with ethyl acetate (20 mL×2). After that, the organic layers were washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (n-hexane/ethyl acetate=5/1) to give the title compound as a white solid (3.23 g, yield 62%).
Reaction SMILES: [CH3:1][C:2]1[C:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[C:6]([CH3:16])[N:5]=[C:4]([O:17][CH2:18][C:19]([N:21]([CH3:28])[CH:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[O:20])[N:3]=1.[C:29]1(Br)[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH3:37])=[CH:31][CH:30]=1>>[CH3:16][C:6]1[C:7]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:12])[CH3:13])=[C:2]([CH3:1])[N:3]=[C:4]([O:17][CH2:18][C:19]([N:21]([CH3:28])[CH:22]2[CH2:23][CH2:24][N:25]([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH2:36][CH3:37])=[CH:31][CH:30]=3)[CH2:26][CH2:27]2)=[O:20])[N:5]=1
Reactant: CCOc1ccc(Br)cc1
Reactant: Cc1nc(OCC(=O)N(C)C2CCNCC2)nc(C)c1NC(=O)OC(C)(C)C
Product: CCOc1ccc(N2CCC(N(C)C(=O)COc3nc(C)c(NC(=O)OC(C)(C)C)c(C)n3)CC2)cc1

Procedure:
The title compound was synthesized from Compound 31 and phenetyl bromide in the same manner as in Example 32.
Reaction SMILES: [Cl:1][C:2]([Cl:13])([Cl:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7](O)=[O:8])=[CH:5][CH:4]=1.S(Cl)([Cl:16])=O>>[Cl:1][C:2]([Cl:13])([Cl:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([Cl:16])=[O:8])=[CH:5][CH:4]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1ccc(C(Cl)(Cl)Cl)cc1
Product: O=C(Cl)c1ccc(C(Cl)(Cl)Cl)cc1

Procedure:
Reaction of 4-trichloromethylbenzoic acid with thionyl chloride affords 4-trichloromethylbenzoyl chloride, which, on reaction with diethylamine, affords 4-trichloro-methyl-N,N-diethylbenzamide. Following a procedure similar to that described in Preparation 5, reaction of the latter with s-butyl lithium and reaction of the resulting lithium salt with sulfur dioxide followed by sodium hydroxylamine-O-sulfonate affords 4-trichloromethyl-2-aminosulfonyl-N,N-diethylbenzamide, which, on heating in glacial acetic acid, affords 6-trichloromethylsaccharin.
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[C:6]([CH3:11])[C:5]=1[OH:12].[Cl:13][C:14]1[N:15]=[C:16](Cl)[C:17]2[S:22][CH:21]=[CH:20][C:18]=2[N:19]=1>C1COCC1.O>[Cl:13][C:14]1[N:15]=[C:16]([O:12][C:5]2[C:6]([CH3:11])=[CH:7][C:8]([CH3:10])=[CH:9][C:4]=2[CH3:3])[C:17]2[S:22][CH:21]=[CH:20][C:18]=2[N:19]=1
Reactant: Clc1nc(Cl)c2sccc2n1
Reactant: Cc1cc(C)c(O)c(C)c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1cc(C)c(Oc2nc(Cl)nc3ccsc23)c(C)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 55.9 %

Procedure:
A stirred suspension of NaH (7.8 mg, 0.19 mmol) in dry THF (1 mL) was added 2,4,6-trimethyl phenol (26.4 mg, 0.19 mmol) and stirred at room temperature for 30 min under Argon. The reaction mixture was added to a solution of 2,4-dichlorothieno[3,2-d]pyrimidine (39.6 mg, 0.19 mmol) in dry THF (1 mL) at 0° C. and allow it to slowly warmed up to room temperature. After stirring the reaction for 4 h, the resulting mixture was diluted with water and washed with EtOAc. The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (9:1) to give the product as a white solid (32.4 mg, 56%):
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][CH2:12][C:13](O)=O)=[CH:2]1.O.ON1C2C=CC=CC=2N=N1.C(N=C=NC(C)C)(C)C.Cl.[O:37]1[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=2[O:40][CH2:39][CH:38]1[CH2:47][NH2:48]>CN(C=O)C>[O:37]1[C:42]2[CH:43]=[CH:44][CH:45]=[CH:46][C:41]=2[O:40][CH2:39][CH:38]1[CH2:47][NH:48][CH2:13][CH2:12][CH2:11][CH2:10][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1
Reactant: O=C(O)CCCc1c[nH]c2ccccc12
Reactant: NCC1COc2ccccc2O1
Agent: CC(C)N=C=NC(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Product: c1ccc2c(c1)OCC(CNCCCCc1c[nH]c3ccccc13)O2
Temperature: 25 °C
Reaction time: 2 h
Yield: 59.4 %

Procedure:
3-Indolebutyric acid (1.2 g, 6.0 mmole), 1-hydroxybenzotriazole hydrate (0.97 g, 7.2 mmole) and 1,3-diisopropylcarbodiimide (2.3 ml, 14.4 mmole) were combined in 100 ml of DMF and stirred at room temperature for 2 hours under a nitrogen atmosphere. To this was added dropwise 2,3-dihydro-1,4-benzodioxin-2methanamine hydrochloride (1.2 g, 6.0 mmole) in 50 ml of DMF and the mixture was further stirred for 24 hours. The solvent was removed and the residue partitioned between dichloromethane and water. The separated dichloromethane layer was dried over anhydrous sodium sulfate, filtered and concentrated in vacuum. The residue was chromatographed on a silica gel column using ethyl acetate as the eluant. Fractions were concentrated and washed with a minimum amount of THF to remove a by-product and to give 1.2 g (57%) of the desired product, (2,3-dihydro-benzo [1,4]dioxin-2-ylmethyl)-4-(1H-indol-3-yl)-butanamide, as an oil.
Reaction SMILES: P(Br)(Br)[Br:2].[CH2:5](O)[C:6]#[C:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]>CCOCC.N1C=CC=CC=1>[Br:2][CH2:5][C:6]#[C:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11]/[CH:12]=[CH:13]\[CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCC/C=C\C/C=C\CC#CCO
Reactant: BrP(Br)Br
Solvent: CCOCC
Solvent: c1ccncc1
Product: CCCCC/C=C\C/C=C\CC#CCBr
Temperature: 23 °C
Yield: 236.2 %

Procedure:
A solution of phosphorous tribromide (0.47 g, 1.73 mmol) in absolute ether (0.5 ml) was added dropwise during five minutes to a mixture of (Z,Z)-5,8-tetradecadien-2-yn-1-ol (1.03 g, 5 mmol), and dry pyridine (14 mg, 0.18 mmol) in 8 ml of absolute ether. The reaction mixture was heated under reflux for 2.5 h, cooled to 23° C., then poured onto ice-water. It was extracted three times with ether. The combined ether extracts were washed with dilute aqueous sodium bicarbonate solution, water, dried over Na2SO4 and concentrated in vacuo. Evaporative distillation of the crude product at 145°-148° C./0.15 mm afforded 1.1 g (80.5%) of (Z,Z)-1-bromo-5,8-tetradecadien-2-yne as a pale yellow oil.
Reaction SMILES: COC1C=CC2CC3C(=O)C(C)(C=2C=1)CCCC3.Cl[CH2:20][CH2:21][CH2:22][CH2:23][C:24]1([CH3:37])[C:33]2[C:28](=[CH:29][C:30]([O:34][CH3:35])=[CH:31][CH:32]=2)[CH2:27][CH2:26][C:25]1=[O:36]>>[CH3:35][O:34][C:30]1[CH:31]=[CH:32][C:33]2[C:24]3([CH3:37])[C:25](=[O:36])[CH:26]([CH2:20][CH2:21][CH2:22][CH2:23]3)[CH2:27][C:28]=2[CH:29]=1
Reactant: COc1ccc2c(c1)CCC(=O)C2(C)CCCCCl
Agent: COc1ccc2c(c1)C1(C)CCCCC(C2)C1=O
Product: COc1ccc2c(c1)CC1CCCCC2(C)C1=O

Procedure:
Using a procedure analogous to that described in Example X for the preparation of 6,7,8,9,10,11-hexahydro-3-methoxy-5-methyl-5,10-methano-5H-benzocyclononen-12-one, there is obtained from 30.5 g. of 1-(4-chlorobutyl)-1-methyl-6-methoxy-2-tetralone 15 g. of the title product, b.p. 140° to 145° C. (0.5 mm.). I. R. Analysis: 5.82, 8.05 μ.
Reaction SMILES: [OH-].[Na+].O.[CH2:4]([SH:6])[CH3:5].[CH3:7][C:8]1([CH3:31])[O:12][N:11]=[C:10]([S:13][CH2:14][C:15]2[C:16]([C:27]([F:30])([F:29])[F:28])=[N:17][N:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:19]=2F)[CH2:9]1>CN(C)C=O>[CH3:7][C:8]1([CH3:31])[O:12][N:11]=[C:10]([S:13][CH2:14][C:15]2[C:16]([C:27]([F:30])([F:29])[F:28])=[N:17][N:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:19]=2[S:6][CH2:4][CH3:5])[CH2:9]1
Reactant: CC1(C)CC(SCc2c(C(F)(F)F)nn(-c3ccccc3)c2F)=NO1
Reactant: CCS
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CN(C)C=O
Product: CCSc1c(CSC2=NOC(C)(C)C2)c(C(F)(F)F)nn1-c1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 103.1 %

Procedure:
0.2 g (4.0 mmoles) of sodium hydroxide and 1 ml of water were added to a solution of 0.25 g (4.0 mmoles) of ethanethiol dissolved in 10 ml of N,N-dimethylformamide. The mixture was stirred at room temperature for 30 minutes. Thereto was added a solution of 0.5 g (1.4 mmoles) of 5,5-dimethyl-3-(5-fluoro-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline dissolved in 5 ml of N,N-dimethylformamide. The resulting mixture was stirred for 1 hour to give rise to a reaction. After the completion of the reaction, the reaction mixture was poured into water, followed by extraction with ethyl acetate. The resulting organic layer was washed with an aqueous sodium chloride solution and then dried over anhydrous magnesium sulfate. The resulting solution was subjected to vacuum distillation to remove the solvent contained therein, to obtain 0.6 g (yield: 100%) of 5,5-dimethyl-3-(5-ethylthio-1-phenyl-3-trifluoromethyl-1H-pyrazol-4-ylmethylthio)-2-isoxazoline.
Reaction SMILES: [CH2:1]1[O:12][C:11]2[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=2[O:2]1.[NH2:13][C:14]1[CH:23]=[CH:22][C:21]2[C:16](=[N:17][C:18]([Cl:24])=[CH:19][CH:20]=2)[N:15]=1>O.C(O)CC>[Cl:24][C:18]1[N:17]=[C:16]2[C:21]([CH:22]=[CH:23][C:14]([NH:13][C:6](=[O:8])[C:5]3[CH:9]=[CH:10][C:11]4[O:12][CH2:1][O:2][C:3]=4[CH:4]=3)=[N:15]2)=[CH:20][CH:19]=1
Reactant: Nc1ccc2ccc(Cl)nc2n1
Reactant: O=C(O)c1ccc2c(c1)OCO2
Solvent: O
Solvent: CCCO
Product: O=C(Nc1ccc2ccc(Cl)nc2n1)c1ccc2c(c1)OCO2
Temperature: 4 °C
Yield: 39.3 %

Procedure:
The procedure is similar to that described in Example 1, but starting with 3,4-methylenedioxybenzoic acid (16.6 g), N,N'-carbonyldiimidazole (16.2 g) and 2-amino-7-chloro-1,8-naphthyridine (11.7 g). The product produced by precipitation in water (15.7 g; m.p. 256° C.) is dissolved in 1-propanol (1000 cc). After 16 hours' cooling at 4° C., the crystallised solid is separated by filtration, washed with 1-propanol (3×20 cc) and dried at 40° C. under reduced pressure (0.067 kPa). N-(7-chloro-1,8-naphthyridin-2-yl)-3,4-methylenedioxybenzamide (8.4 g) is produced, m.p. 256° C.