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

HRID 1808835ノート

反応式

HRID 1808835 の反応式
[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

参加物

11

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 887Methanol溶媒2 回HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-5b5c6bec9bfe44aba60f1d0179af14a3
出典データセット
uspto-grants-2013_01
特許番号
US08361998B2

反応ノート

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