(1R,2S)-Tranylcypromine → Methyl 4-{[3-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)-1-pyrrolidinyl]methyl}benzoate

HRID 529315

반응식

HRID 529315 반응식
[C:1]1([C@@H:7]2[CH2:9][C@H:8]2[NH2:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:11]([CH:13]1[CH2:17][CH2:16][N:15]([CH2:18][C:19]2[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=2)[CH2:14]1)=O.C([BH3-])#N.[Na+]>CO>[C:1]1([C@@H:7]2[CH2:9][C@H:8]2[NH:10][CH2:11][CH:13]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=3)[CH2:14]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

참가 물질

5

반응물 3

HCID 19493(1R,2S)-TranylcypromineHCID 5003444Sodium cyanoborohydrideHCID 86708239Methyl 4-((3-formylpyrrolidin-1-yl)methyl)benzoate

생성물 1

HCID 68385362Methyl 4-{[3-({[(1R,2S)-2-phenylcyclopropyl]amino}methyl)-1-pyrrolidinyl]methyl}benzoate수율 40.6%

시약·촉매·용매 1

HCID 887Methanol용매

실험 절차

A solution of (1R,2S)-2-phenylcyclopropanamine (300 mg, 2.252 mmol) and methyl 4-((3-formylpyrrolidin-1-yl)methyl)benzoate (501 mg, 2.027 mmol) in methanol (50 mL) was heated to reflux for 5 minutes. The reaction mixture was cooled to room temperature and sodium cyanoborohydride (212 mg, 3.38 mmol) was added. The reaction was stirred at room temperature for 16 hours. After concentrating, dichloromethane was added and the solution was washed with water, dried over MgSO4, filtered and concentrated. HPLC purification (reverse phase) was performed with a Gemini NX 5u C18 110A, AXIA. 100×30.00 mm 5 micron column. A 7 minute gradient run (0% AcCN/H2O, 0.1% Formic Acid to 55% ACN/H2O, 0.1% Formic Acid) with UV detection at 214 nm was utilized. Added 1 ml of 1N HCl to fractions containing product and concentrated. Only the desired ester was seen by LC/MS of fractions before concentrating. Obtained 300 mg of a mixture of diastereomers.

후처리

  1. temperatureto reflux for 5 minutes
  2. concentrationAfter concentrating
  3. additiondichloromethane was added
  4. washthe solution was washed with water
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customHPLC purification (reverse phase)
  9. customA 7 minute gradient run (0% AcCN/H2O, 0.1% Formic Acid to 55% ACN/H2O, 0.1% Formic Acid)
  10. additionAdded 1 ml of 1N HCl to fractions
  11. additioncontaining product
  12. concentrationconcentrated
  13. concentrationbefore concentrating

출처 및 근거

ORD 기록
ord-3856b23c77d449aebf03d8305e376665
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09346840B2

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