Lithium hydroxide, monohydrate → 5-[(3-{[(1S)-1-(hydroxymethyl)propyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylic acid

HRID 1989968Notes

Reaction equation

HRID 1989968 reaction equation
O.[OH-].[Li+].[OH:4][CH2:5][C@@H:6]([O:9][C:10]1[CH:11]=[C:12]([O:25][C:26]2[N:27]=[CH:28][C:29]([C:32]([O:34]C)=[O:33])=[N:30][CH:31]=2)[CH:13]=[C:14]([C:16]([NH:18][C:19]2[CH:23]=[CH:22][N:21]([CH3:24])[N:20]=2)=[O:17])[CH:15]=1)[CH2:7][CH3:8]>O.C1COCC1>[OH:4][CH2:5][C@@H:6]([O:9][C:10]1[CH:11]=[C:12]([O:25][C:26]2[N:27]=[CH:28][C:29]([C:32]([OH:34])=[O:33])=[N:30][CH:31]=2)[CH:13]=[C:14]([C:16]([NH:18][C:19]2[CH:23]=[CH:22][N:21]([CH3:24])[N:20]=2)=[O:17])[CH:15]=1)[CH2:7][CH3:8]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 59127088methyl 5-[(3-{[(1S)-1-(hydroxymethyl)propyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylate

Product 1

HCID 536296535-[(3-{[(1S)-1-(hydroxymethyl)propyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylic acidYield 46.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Lithium hydroxide monohydrate (6 mg, 0.14 mmol) in water (1 mL) was added to a solution of methyl 5-[(3-{[(1S)-1-(hydroxymethyl)propyl]oxy}-5-{[(1-methyl-1H-pyrazol-3-yl)amino]carbonyl}phenyl)oxy]pyrazine-2-carboxylate (25 mg, 0.06 mmol) in THF (1 mL). The mixture was allowed to stir at RT for 16 hours. The THF was removed in vacuo and the resulting solution was partitioned between water (10 mL) and ethyl acetate (25 mL), the ethyl acetate layer was washed with brine (10 mL) and dried (MgSO4). The aqueous layer was then adjusted to pH 7 by addition of 1M hydrochloric acid and extracted with ethyl acetate (25 mL). The ethyl acetate layer was washed with brine (10 mL) and dried (MgSO4). The ethyl acetate extracts were combined and evaporated to give the required product (12 mg). m/z 428.44 (M+H)+

Workup

  1. customThe THF was removed in vacuo
  2. customthe resulting solution was partitioned between water (10 mL) and ethyl acetate (25 mL)
  3. washthe ethyl acetate layer was washed with brine (10 mL)
  4. dry with materialdried (MgSO4)
  5. additionThe aqueous layer was then adjusted to pH 7 by addition of 1M hydrochloric acid
  6. extractionextracted with ethyl acetate (25 mL)
  7. washThe ethyl acetate layer was washed with brine (10 mL)
  8. dry with materialdried (MgSO4)
  9. customevaporated

Sources & evidence

ORD record
ord-0ee0069594354c23a522ca8c13f1e71a
Source dataset
uspto-grants-2010_01
Patent number
US07642263B2

Reaction notes

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