Sodium Hydroxide → [1-(1-amino-7-isoquinolinylmethyl)-2-oxopyrrolidin-3-(S)yl]carbamic acid tert-butyl ester

HRID 1279076ノート

反応式

HRID 1279076 の反応式
[NH:1]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C@H:2]([C:7](OCC1C=CC=CC=1)=[O:8])[CH2:3][C:4](=O)O.[NH2:24][C:25]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([CH2:35][NH2:36])[CH:33]=2)[CH:28]=[CH:27][N:26]=1.C([BH3-])#N.[Na+].[OH-].[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[C:20]([O:19][C:17](=[O:18])[NH:1][C@H:2]1[CH2:3][CH2:4][N:36]([CH2:35][C:32]2[CH:33]=[C:34]3[C:29]([CH:28]=[CH:27][N:26]=[C:25]3[NH2:24])=[CH:30][CH:31]=2)[C:7]1=[O:8])([CH3:21])([CH3:22])[CH3:23]

参加物

7

反応物 4

HCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 7017887(3S)-4-(benzyloxy)-3-(((tert-butoxy)carbonyl)amino)-4-oxobutanoic acidHCID 226658411-Amino-7-isoquinolinemethanamine

生成物 1

HCID 54531194[1-(1-amino-7-isoquinolinylmethyl)-2-oxopyrrolidin-3-(S)yl]carbamic acid tert-butyl ester収率 44.2%

試薬・触媒・溶媒 2

HCID 3007855Zincchloride触媒HCID 887Methanol溶媒2 回

実験手順

To a solution of 0.3 g of Boc-L-Asp(H)-OBn (WO 96/40679) dissolved in 2 mL methanol was added 176 mg of 1-amino-7-(aminomethyl)isoquinoline. After stirring for 30 minutes, a solution of 80 mg sodium cyanoborohydride and 90 mg zinc chloride in 2 mL methanol was added. The mixture was stirred for an additional two hours. After this time, 7 mL of an aqueous 0.2 N sodium hydroxide solution was added and the resulting mixture was concentrated. The residue was treated with 100 mL dichloromethane and 10 mL water, filtered and an additional 100 mL water was added to the filtrate. The organic layer was separated and washed with aqueous 5% sodium hydrogencarbonate and brine. All aqueous layers were washed twice with dichloromethane. The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by column chromatography on silica gel eluting with a gradient of ethyl acetate/dichloromethane/methanol=10/10/1 to dichloromethane/methanol=10/1 to give 146 mg of the title compound.

後処理

  1. stirringThe mixture was stirred for an additional two hours
  2. concentrationthe resulting mixture was concentrated
  3. additionThe residue was treated with 100 mL dichloromethane and 10 mL water
  4. filtrationfiltered
  5. additionan additional 100 mL water was added to the filtrate
  6. customThe organic layer was separated
  7. washwashed with aqueous 5% sodium hydrogencarbonate and brine
  8. washAll aqueous layers were washed twice with dichloromethane
  9. dry with materialThe combined organic layers were dried over sodium sulfate
  10. concentrationconcentrated
  11. customThe residue was purified by column chromatography on silica gel eluting with a gradient of ethyl acetate/dichloromethane/methanol=10/10/1 to dichloromethane/methanol=10/1

出典と根拠

ORDレコード
ord-a852e3917ee94092b9f0639dc01f4ac8
出典データセット
uspto-grants-2002_09
特許番号
US06444672B1

反応ノート

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