Methanol → (R)-5-(2-(5-fluoro-2-methylpyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

HRID 1631308Notes

Reaction equation

HRID 1631308 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:13][CH2:12][CH2:11][N:10]2[C:14]2[CH:19]=[CH:18][N:17]3[N:20]=[CH:21][C:22]([C:23]([O:25]CC)=[O:24])=[C:16]3[N:15]=2)[C:5]([CH3:8])=[N:6][CH:7]=1.C1COCC1.CO.O.[OH-].[Li+]>O>[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[CH2:13][CH2:12][CH2:11][N:10]2[C:14]2[CH:19]=[CH:18][N:17]3[N:20]=[CH:21][C:22]([C:23]([OH:25])=[O:24])=[C:16]3[N:15]=2)[C:5]([CH3:8])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 86664567(R)-ethyl 5-(2-(5-fluoro-2-methylpyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

Product 1

HCID 66853615(R)-5-(2-(5-fluoro-2-methylpyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acidYield 86%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of (R)-ethyl 5-(2-(5-fluoro-2-methylpyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (480 mg, 1.3 mmol) in a 1:1:1 mixture of THF:MeOH:water (30 mL) was added lithium hydroxide monohydrate (164 mg, 3.9 mmol). The mixture was stirred at ambient temperature for 16 hours then concentrated to ⅓ volume, acidified to pH 3 with 1N HCl and extracted with EtOAc (3×30 mL). The combined organic phases were washed with brine (20 mL), dried over Na2SO4, filtered and concentrated to afford the title product as a white solid (381 mg, 86% yield). MS (apci) m/z=342.0 (M+H).

Workup

  1. concentrationthen concentrated
  2. extractionextracted with EtOAc (3×30 mL)
  3. washThe combined organic phases were washed with brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-ddcb2cb8db284a9b95e93fcf7447fc11
Source dataset
uspto-grants-2014_07
Patent number
US08791123B2

Reaction notes

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