Acetic Acid → (S)-4-Chloro-N-cyclopentyl-N-(3-methyl-1-(pyrrolidin-1-yl)butan-2-yl)benzamide

HRID 1808835노트

반응식

HRID 1808835 반응식
[C:1]1(=O)[CH2:5][CH:4]=[CH:3][CH2:2]1.[CH3:7][CH:8]([CH3:17])[C@H:9]([NH2:16])[CH2:10][N:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1.C([BH3-])#N.[Na+].C(O)(=O)C.CCN(C(C)C)C(C)C.[Cl:35][C:36]1[CH:44]=[CH:43][C:39]([C:40](Cl)=[O:41])=[CH:38][CH:37]=1>C1COCC1.C(Cl)Cl.CO.O>[Cl:35][C:36]1[CH:44]=[CH:43][C:39]([C:40]([N:16]([CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[C@@H:9]([CH:8]([CH3:17])[CH3:7])[CH2:10][N:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[O:41])=[CH:38][CH:37]=1

참가 물질

11

반응물 6

HCID 176Acetic AcidHCID 85014-Chlorobenzoyl chlorideHCID 81531DiisopropylethylamineHCID 84351Cyclopent-3-en-1-oneHCID 5003444Sodium cyanoborohydrideHCID 22689455(S)-3-methyl-1-(pyrrolidin-1-yl)butan-2-amine

생성물 1

HCID 67772988(S)-4-Chloro-N-cyclopentyl-N-(3-methyl-1-(pyrrolidin-1-yl)butan-2-yl)benzamide수율 7%

시약·촉매·용매 4

HCID 887Methanol용매2회HCID 962Water용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회

실험 절차

Cyclopent-3-enone (57.9 mg, 0.70 mmol) was added to a mixture of (S)-3-methyl-1-(pyrrolidin-1-yl)butan-2-amine (109 mg, 0.70 mmol), which is commercially available, in THF (1.7 mL). After 10 min was a solution of sodium cyanoborohydride (58 mg, 0.92 mmol) in THF (0.9 mL) added. The resultant mixture was stirred at rt for 3 h. Acetic acid (0.3 mL, 5.24 mmol) and MeOH (2 mL) was added and the mixture stirred at rt overnight. The reaction mixture was concentrated and the residue dissolved in DMF (2.5 mL). DIPEA (0.5 mL, 2.86 mmol) and a solution of 4-chlorobenzoyl chloride (2.2 mL, 1.01 mmol) in DCM (2 mL) was added. The resultant mixture was stirred at rt overnight. H2O (0.5 mL) and MeOH (5 mL) were added and the mixture was stirred for 10 min. The solvent was removed under reduced pressure and the residue mixed in NaOH (1 N aq., 10 mL). The water layer was extracted with DCM (3×10 mL) and the combined organic layer were washed with brine (10 mL), filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (17 mg, 7%).

후처리

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue dissolved in DMF (2.5 mL)
  3. stirringthe mixture was stirred for 10 min
  4. customThe solvent was removed under reduced pressure
  5. additionthe residue mixed in NaOH (1 N aq., 10 mL)
  6. extractionThe water layer was extracted with DCM (3×10 mL)
  7. washthe combined organic layer were washed with brine (10 mL)
  8. filtrationfiltered through a phase separator
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by preparative HPLC

출처 및 근거

ORD 기록
ord-5b5c6bec9bfe44aba60f1d0179af14a3
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08361998B2

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