Sodium Hydroxide → N,beta,beta-trimethyl-L-phenylalanyl-N1-{(1S,2E)-1-isopropyl-4-[methoxy(methyl)-amino]-3-methyl-4-oxobut-2-enyl}-N1,3-dimethyl-L-valinamide

HRID 133807

反応式

HRID 133807 の反応式
[CH3:1][NH:2][C@H:3]([C:13]([NH:15][C@H:16]([C:21]([N:23]([C@@H:25]([CH:32]([CH3:34])[CH3:33])/[CH:26]=[C:27](/[C:29]([OH:31])=O)\[CH3:28])[CH3:24])=[O:22])[C:17]([CH3:20])([CH3:19])[CH3:18])=[O:14])[C:4]([CH3:12])([CH3:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.Cl.[CH3:36][NH:37][O:38][CH3:39].[OH-].[Na+]>O1CCCC1.O.[Cl-].[Na+].O>[CH3:1][NH:2][C@H:3]([C:13]([NH:15][C@H:16]([C:21]([N:23]([C@@H:25]([CH:32]([CH3:34])[CH3:33])/[CH:26]=[C:27](\[CH3:28])/[C:29]([N:37]([O:38][CH3:39])[CH3:36])=[O:31])[CH3:24])=[O:22])[C:17]([CH3:18])([CH3:20])[CH3:19])=[O:14])[C:4]([CH3:12])([CH3:11])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

参加物

7

反応物 3

HCID 14798Sodium Hydroxide2 回HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 6918637N,beta,beta-Trimethyl-L-phenylalanyl-N-((1S,2E)-3-carboxy-1-(1-methylethyl)-2-buten-1-yl)-N,3-dimethyl-L-valinamide

生成物 1

HCID 11656496N,beta,beta-trimethyl-L-phenylalanyl-N1-{(1S,2E)-1-isopropyl-4-[methoxy(methyl)-amino]-3-methyl-4-oxobut-2-enyl}-N1,3-dimethyl-L-valinamide収率 95%

試薬・触媒・溶媒 3

HCID 962Water溶媒2 回HCID 8028Tetrahydrofuran溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

A solution of N,β,β-trimethyl-L-phenylalanyl-N1-[(1S,2E)-3-carboxy-1-isopropylbut-2-enyl]-N1,3-dimethyl-L-valinamide (473 mg, 1 mmol, WO 99/32509) in tetrahydrofuran (2 mL) is added a solution of N,O-dimethylhydroxylamine hydrochloride (166 mg, 1.7 mmol) in water (2 mL), adjusting the reaction mixture to pH 4.5 by adding dropwise 1.0 N sodium hydroxide solution. To this is added dropwise a solution of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimine hydrochloride (479 mg, 2.5 mmol) in water (7 mL) over a period of 7 min, maintaining pH 4.5 by using 1.0 N sodium hydroxide solution. The reaction mixture is stirred at room temperature for 2.5 h, adjusting the pH to 6-7. To this is added brine (10 mL) and extracted with dichloromethane. The combined organic layers are washed with brine, dried (Na2SO4), filtered and concentrated to give 491 mg (95%) of the title compound as a white solid. HRMS (ESI) calcd for C29H48N4O4 (M+H+) 517.3748, found 517.3750.

後処理

  1. temperaturemaintaining pH 4.5
  2. extractionextracted with dichloromethane
  3. washThe combined organic layers are washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-47f1c2a29b7147a8966671c671391628
出典データセット
uspto-grants-2008_06
特許番号
US07390910B2

関連ノート

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