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 880615Notes

Reaction equation

HRID 880615 reaction equation
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]

Participants

6

Reactant 2

HCID 3939Lithium Hydroxide2×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

Product 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 acidYield 70%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

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%).

Workup

  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

Sources & evidence

ORD record
ord-257473b673894136b1fc297c159132ec
Source dataset
uspto-grants-2015_03
Patent number
US08993523B2

Reaction notes

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