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

HRID 534167

反応式

HRID 534167 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-dbce40f3c65743679ec132f79f0a15d1
出典データセット
uspto-grants-2014_10
特許番号
US08853408B2

関連ノート

読み込み中…