Lithium Hydroxide → 1-[5-((S)-1-{(S)-2-[(S)-2-(tert-Butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-pyrrolidin-2-yl)-pyridin-3-yl]-1H-indole-3-carboxylic acid

HRID 880615ノート

反応式

HRID 880615 の反応式
C([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:8]([C:15]2[CH:16]=[N:17][CH:18]=[C:19]([C@@H:21]3[CH2:25][CH2:24][CH2:23][N:22]3[C:26](=[O:45])[C@@H:27]([NH:31][C:32](=[O:44])[C@@H:33]([N:35]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH3:36])[CH3:34])[CH:28]([CH3:30])[CH3:29])[CH:20]=2)[CH:7]=1)=[O:5])C.[Li+].[OH-]>C1COCC1.CO.O>[C:40]([O:39][C:37]([N:35]([CH3:36])[C@@H:33]([CH3:34])[C:32]([NH:31][C@@H:27]([CH:28]([CH3:29])[CH3:30])[C:26]([N:22]1[CH2:23][CH2:24][CH2:25][C@H:21]1[C:19]1[CH:20]=[C:15]([N:8]2[C:9]3[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:6]([C:4]([OH:5])=[O:3])=[CH:7]2)[CH:16]=[N:17][CH:18]=1)=[O:45])=[O:44])=[O:38])([CH3:43])([CH3:42])[CH3:41]

参加物

6

反応物 2

HCID 3939Lithium Hydroxide2 回HCID 679736671-[5-((S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-pyrrolidin-2-yl)-pyridin-3-yl]-1H-indole-3-carboxylic acid ethyl ester

生成物 1

HCID 679737641-[5-((S)-1-{(S)-2-[(S)-2-(tert-Butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-pyrrolidin-2-yl)-pyridin-3-yl]-1H-indole-3-carboxylic acid収率 70%

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a solution of 1-[5-((S)-1-{(S)-2-[(S)-2-(tert-butoxycarbonyl-methyl-amino)-propionylamino]-3-methyl-butyryl}-pyrrolidin-2-yl)-pyridin-3-yl]-1H-indole-3-carboxylic acid ethyl ester (I-2A-2c: 0.29 g, 0.46 mmol) in THF (1 mL) and MeOH (0.3 mL) was added a solution of LiOH (0.035 g, 0.80 mmol) in water (0.3 mL). The resulting mixture was stirred at room temperature for 5 hours. More LiOH (0.065 g, 2.70 mmol) was added and stirring continued for overnight. The reaction mixture was then concentrated under reduced pressure to remove all organic solvents, then diluted with water. To this mixture 1 M HCl was added dropwise until pH=4. The white precipitate formed was filtered and dried in vacuo to give the titled compound as a white powder (0.19 g, 70%).

後処理

  1. stirringstirring
  2. waitcontinued for overnight
  3. concentrationThe reaction mixture was then concentrated under reduced pressure
  4. customto remove all organic solvents
  5. additiondiluted with water
  6. additionTo this mixture 1 M HCl was added dropwise until pH=4
  7. customThe white precipitate formed
  8. filtrationwas filtered
  9. customdried in vacuo

出典と根拠

ORDレコード
ord-257473b673894136b1fc297c159132ec
出典データセット
uspto-grants-2015_03
特許番号
US08993523B2

反応ノート

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