Ethanol → (+/-)-3-(4-fluorophenyl)-2-(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid

HRID 505716노트

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HRID 505716 반응식
[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH:6]=[C:7]2[CH2:16][CH2:15][C:14]3[CH:13]=[C:12]([C:17]([O:19]CC)=[O:18])[CH:11]=[CH:10][C:9]=3[C:8]2=O)=[CH:4][CH:3]=1.[NH:25]([C:27]1[CH:28]=[C:29]2[C:34](=[CH:35][CH:36]=1)[C:33](=[O:37])[NH:32][CH2:31][CH2:30]2)[NH2:26].C(O)C.[O-]CC.[Na+]>CN(C)C=O>[F:1][C:2]1[CH:24]=[CH:23][C:5]([CH:6]2[CH:7]3[C:8]([C:9]4[CH:10]=[CH:11][C:12]([C:17]([OH:19])=[O:18])=[CH:13][C:14]=4[CH2:15][CH2:16]3)=[N:26][N:25]2[C:27]2[CH:28]=[C:29]3[C:34](=[CH:35][CH:36]=2)[C:33](=[O:37])[NH:32][CH2:31][CH2:30]3)=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 702Ethanol3회HCID 2723922Sodium ethoxideHCID 2740454Ethyl 6-(4-fluorobenzylidene)-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylateHCID 129719656-Hydrazinyl-3,4-dihydroisoquinolin-1(2H)-one

생성물 1

HCID 59429347(+/-)-3-(4-fluorophenyl)-2-(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid수율 63%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
80 °C

실험 절차

To ethyl 6-(4-fluorobenzylidene)-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate (Preparation 16; 303 mg, 1.07 mmol) and 6-hydrazinyl-3,4-dihydroisoquinolin-1(2H)-one (240 mg, 1.3 mmol) (U.S. Pat. No. 6,432,974, Kelly et al., Aug. 13, 2002, intermediate 2) was added ethanol (8 mL) and 21% sodium ethoxide in ethanol (1.5 mL, 4 mmol) in a vial. The vial was flushed with argon and heated at 80° C. overnight with stirring. The reaction was quenched with 1M hydrogen chloride (8 mL) and diluted with water to give a precipitate. The precipitate was collected by vacuum filtration to give a yellow solid. The solid was dissolved in of dimethylformamide (3 mL) and purified by reverse phase chromatography with 45-75% acetonitrile/water to give (±)-3-(4-fluorophenyl)-2-(1-oxo-1,2,3,4-tetrahydroisoquinolin-6-yl)-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid as a 25/75 mixture of the cis/trans-diastereomers (290 mg, 0.68 mmol, 63% yield). ES-MS m/z 430 (M+H).

후처리

  1. customThe vial was flushed with argon
  2. customThe reaction was quenched with 1M hydrogen chloride (8 mL)
  3. additiondiluted with water
  4. customto give a precipitate
  5. filtrationThe precipitate was collected by vacuum filtration
  6. customto give a yellow solid
  7. custompurified by reverse phase chromatography with 45-75% acetonitrile/water

출처 및 근거

ORD 기록
ord-e46227d7cbcd4e45a2dce678b79e8f98
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07781428B2

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