trans-2-Aminomethyl-1-cyclohexanol → HCID 20788997、化合物

HRID 1272762ノート

反応式

HRID 1272762 の反応式
C([N:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13](Cl)=[O:14])=[CH:10][CH:11]=2)[C:6]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[N:5]1)(=O)C.[NH2:23][CH2:24][C@@H:25]1[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]1[OH:31]>N1C=CC=CC=1>[OH:31][C@@H:26]1[CH2:27][CH2:28][CH2:29][CH2:30][CH:25]1[CH2:24][NH:23][C:13]([C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][CH:10]=1)[NH:4][N:5]=[C:6]2[C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=1)=[O:14]

参加物

4

反応物 2

HCID 2724658trans-2-Aminomethyl-1-cyclohexanolHCID 224802271-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carbonyl chloride

生成物 1

HCID 20788997HCID 20788997、化合物収率 69%

試薬・触媒・溶媒 1

HCID 1049Pyridine溶媒

反応条件

温度
60 °C

実験手順

To a flask containing 1-acetyl-3-(4-fluorophenyl)-1H-indazole-5-carbonyl chloride (330 mg, 0.95 mmol) dissolved in pyridine (6 mL) was added trans-2-aminomethyl-1-cyclohexanol (135.6 mg, 1.05 mmol). The reaction was allowed to stir under a nitrogen atmosphere overnight. Solvent was removed and the reaction was extracted with ethyl acetate. The organic phase was washed with a saturated aqueous solution of sodium bicarbonate, dried with magnesium sulfate, filtered and concentrated to yield the crude product. The product was purified by column chromatography (SiO2, 5% methanol in dichloromethane). The compound was taken up in a 3% ammonia in methanol solution (8 mL) and allowed to reflux at 60° C. for three hours. The reaction was neutralized with 1 N HCl solution and extracted with ethyl acetate. The organic layer was dried with magnesium sulfate, filtered and concentrated to yield the title compound (240 mg, 69% yield). 1H NMR (DMSO-d6) δ 13.5 (s, 1H), 8.6 (s, 2H), 8.1 (m, 2H), 7.9 (d, 1H), 7.6 (d, 1H), 7.4 (m, 2H), 4.8 (s, 1H), 3.5 (m, 1H), 3.2 (m, 1H), 1.8 (m, 2H), 1.6 (m, 2H), 1.4 (m, 2H), 0.8–1.0 (m, 3H), ES-MS m/z 368 [M+1]+.

後処理

  1. customSolvent was removed
  2. extractionthe reaction was extracted with ethyl acetate
  3. washThe organic phase was washed with a saturated aqueous solution of sodium bicarbonate
  4. dry with materialdried with magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield the crude product
  8. customThe product was purified by column chromatography (SiO2, 5% methanol in dichloromethane)
  9. extractionextracted with ethyl acetate
  10. dry with materialThe organic layer was dried with magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated

出典と根拠

ORDレコード
ord-cd26253da8d24fcd9b52829c41b9ae30
出典データセット
uspto-grants-2007_04
特許番号
US07208513B2

反応ノート

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