Bromomethylcyclopropane → (3S,5R,6S)-3-((1H-tetrazol-5-yl)methyl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)piperidin-2-one

HRID 1048251노트

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HRID 1048251 반응식
[NH:1]1[C:5]([CH2:6][C@@H:7]2[CH2:12][C@H:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=3)[C@@H:10]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[NH:9][C:8]2=[O:27])=[N:4][N:3]=[N:2]1.[CH3:28][C:29]([CH3:32])([O-])[CH3:30].[Na+].BrCC1CC1>CN(C=O)C>[NH:4]1[C:5]([CH2:6][C@@H:7]2[CH2:12][C@H:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=3)[C@@H:10]([C:20]3[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=3)[N:9]([CH2:28][CH:29]3[CH2:32][CH2:30]3)[C:8]2=[O:27])=[N:1][N:2]=[N:3]1

참가 물질

5

반응물 3

HCID 81503BromomethylcyclopropaneHCID 23676156Sodium t-butoxideHCID 178517874HCID 178517874, 화합물

생성물 1

HCID 178516686(3S,5R,6S)-3-((1H-tetrazol-5-yl)methyl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)piperidin-2-one

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
0 °C

실험 절차

A solution of (3S,5R,6S)-3-((1H-tetrazol-5-yl)methyl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one (Example 60, Step A) (65 mg, 0.162 mmol) in DMF (1.6 mL) was cooled to 0° C. and sodium tert-butoxide (31.1 mg, 0.323 mmol) was added. The reaction mixture was stirred at 0° C. for ten minutes before adding (bromomethyl)cyclopropane (78 μL, 0.808 mmol). The reaction mixture was warmed to room temperature and stirred for 16 hours, quenched with saturated ammonium chloride and diluted with water and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the organic layers were combined, washed with 1M LiCl, sat. aq. NaCl solution, dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by reversed phase preparatory HPLC (column:

후처리

  1. temperatureThe reaction mixture was warmed to room temperature
  2. stirringstirred for 16 hours
  3. customquenched with saturated ammonium chloride
  4. additiondiluted with water and ethyl acetate
  5. extractionThe aqueous layer was extracted with ethyl acetate
  6. washwashed with 1M LiCl, sat. aq. NaCl solution
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by reversed phase preparatory HPLC (column

출처 및 근거

ORD 기록
ord-0faad6a0bf3645dc8a7fa84a3e63ee34
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08569341B2

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