Water → 2-(3-(3-((S)-2-Amino-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydropyrimidin-4-yl)-4-fluorophenylamino)cyclopentyl)acetic acid

HRID 2409184Notes

Reaction equation

HRID 2409184 reaction equation
C[O:2][C:3](=[O:30])[CH2:4][CH:5]1[CH2:9][CH2:8][CH:7]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[C:13]([C@:18]3([CH3:29])[C:23]([CH3:25])([CH3:24])[C:22](=[O:26])[N:21]([CH3:27])[C:20]([NH2:28])=[N:19]3)[CH:12]=2)[CH2:6]1.O.[Li+].[OH-]>C1COCC1.CO>[NH2:28][C:20]1[N:21]([CH3:27])[C:22](=[O:26])[C:23]([CH3:24])([CH3:25])[C@:18]([C:13]2[CH:12]=[C:11]([NH:10][CH:7]3[CH2:8][CH2:9][CH:5]([CH2:4][C:3]([OH:30])=[O:2])[CH2:6]3)[CH:16]=[CH:15][C:14]=2[F:17])([CH3:29])[N:19]=1

Participants

6

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 57516115{3-[3-((S)-2-Amino-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydro-pyrimidin-4-yl)-4-fluoro-phenylamino]-cyclopentyl}-acetic acid methyl ester

Product 1

HCID 575161222-(3-(3-((S)-2-Amino-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydropyrimidin-4-yl)-4-fluorophenylamino)cyclopentyl)acetic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of {3-[3-((S)-2-amino-1,4,5,5-tetramethyl-6-oxo-1,4,5,6-tetrahydro-pyrimidin-4-yl)-4-fluoro-phenylamino]-cyclopentyl}-acetic acid methyl ester (example 95, 0.05 mmol) in THF (1 ml), MeOH (0.3 ml), and H2O (0.3 ml) was added LiOH (1N, 0.1 mmol) and the reaction mixture was stirred at room temperature for 4 h. The mixture was concentrated in vacuo and the residue diluted with aqueous HCl (0.5N) until pH=5 and EtOAc. The white solid which precipitate was filtered off, washed with H2O and dried. The organic phase was dried over Na2SO4 and evaporated to yield a white solid. The combined solid material was triturated with a mixture of dichloromethane and MeOH (10:1), filtered and the filtrate was concentrated in vacuo to yield a mixture of isomers of the title compound as a white solid. MS (ESI): m/z=405.5 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. additionthe residue diluted with aqueous HCl (0.5N) until pH=5 and EtOAc
  3. filtrationThe white solid which precipitate was filtered off
  4. washwashed with H2O
  5. customdried
  6. dry with materialThe organic phase was dried over Na2SO4
  7. customevaporated
  8. customto yield a white solid
  9. customThe combined solid material was triturated with a mixture of dichloromethane and MeOH (10:1)
  10. filtrationfiltered
  11. concentrationthe filtrate was concentrated in vacuo
  12. customto yield

Sources & evidence

ORD record
ord-c61289ff23544a5fa89e0a3c12b2b8f7
Source dataset
uspto-grants-2014_08
Patent number
US08815881B2

Reaction notes

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