Lithium hydroxide, monohydrate → (R)-3-[5-Cyano-1-(1,4-dimethyl-1H-indol-3-ylmethyl)-2-oxo-1,2-dihydro-imidazo[4,5-b]pyridin-3-yl]-3-phenyl-propionic acid

HRID 2175197Notes

Reaction equation

HRID 2175197 reaction equation
C([O:3][C:4](=[O:37])[CH2:5][C@@H:6]([N:13]1[C:17]2=[N:18][C:19]([C:22]#[N:23])=[CH:20][CH:21]=[C:16]2[N:15]([CH2:24][C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][C:32]=3[CH3:34])[N:27]([CH3:35])[CH:26]=2)[C:14]1=[O:36])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)C.O.[OH-].[Li+]>O1CCOCC1.O>[C:22]([C:19]1[N:18]=[C:17]2[N:13]([C@@H:6]([C:7]3[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=3)[CH2:5][C:4]([OH:37])=[O:3])[C:14](=[O:36])[N:15]([CH2:24][C:25]3[C:33]4[C:28](=[CH:29][CH:30]=[CH:31][C:32]=4[CH3:34])[N:27]([CH3:35])[CH:26]=3)[C:16]2=[CH:21][CH:20]=1)#[N:23]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 58497442(R)-3-[5-Cyano-1-(1,4-dimethyl-1H-indol-3-ylmethyl)-2-oxo-1,2-dihydro-imidazo[4,5-b]pyridin-3-yl]-3-phenyl-propionic acid ethyl ester

Product 1

HCID 58497444(R)-3-[5-Cyano-1-(1,4-dimethyl-1H-indol-3-ylmethyl)-2-oxo-1,2-dihydro-imidazo[4,5-b]pyridin-3-yl]-3-phenyl-propionic acidYield 38.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of (R)-3-[5-cyano-1-(1,4-dimethyl-1H-indol-3-ylmethyl)-2-oxo-1,2-dihydro-imidazo[4,5-b]pyridin-3-yl]-3-phenyl-propionic acid ethyl ester (70 mg, 0.14 mmol) in dioxane (4 ml) and water (2 ml) was added lithium hydroxide monohydrate (12 mg, 0.28 mmol) at room temperature. After stirring for 6 hours the reaction appeared to be complete. The reaction was concentrated to a low volume and diluted with water. The reaction mixture was acidified using acetic acid and the resulting precipitate was collected via filtration. The solid was purified once by silica gel flash column chromatography (12 g silica gel, 0-10% MeOH/Dichloromethane) and then again by preparative TLC (2×0.5 mm silica gel, 5% MeOH/Dichloromethane) to afford 25 mg (31%) of the title compound. LCMS, M++1, m/z: 466.43.

Workup

  1. concentrationThe reaction was concentrated to a low volume
  2. additiondiluted with water
  3. filtrationthe resulting precipitate was collected via filtration
  4. customThe solid was purified once by silica gel flash column chromatography (12 g silica gel, 0-10% MeOH/Dichloromethane)

Sources & evidence

ORD record
ord-b9dc1c4824ce4024a341d4eb2f889d9a
Source dataset
uspto-grants-2015_06
Patent number
US09062056B2

Reaction notes

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