Methanol → (S)-5-(1-(5-fluoro-2-methoxypyridin-3-yl)-2-hydroxyethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

HRID 1426958Notes

Reaction equation

HRID 1426958 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:10]2[CH2:14][O:13]C(=O)[N:11]2[C:16]2[CH:21]=[CH:20][N:19]3[N:22]=[CH:23][C:24]([C:25]([O:27]CC)=[O:26])=[C:18]3[N:17]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.CO.C1COCC1.O.[OH-].[Li+]>O>[F:1][C:2]1[CH:3]=[C:4]([C@H:10]([NH:11][C:16]2[CH:21]=[CH:20][N:19]3[N:22]=[CH:23][C:24]([C:25]([OH:27])=[O:26])=[C:18]3[N:17]=2)[CH2:14][OH:13])[C:5]([O:8][CH3:9])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 168937Lithium hydroxide, monohydrateHCID 86691742HCID 86691742, compound

Product 1

HCID 86691743(S)-5-(1-(5-fluoro-2-methoxypyridin-3-yl)-2-hydroxyethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxylic acidYield 45.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of (S)-ethyl 5-(4-(5-fluoro-2-methoxypyridin-3-yl)-2-oxooxazolidin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (311 mg, 0.77 mmol) in a 1:1:1 mixture of MeOH:THF:H2O (15 mL) was added lithium hydroxide monohydrate (97.6 mg, 2.32 mmol). The mixture was stirred at ambient temperature for 16 hours and then at 50° C. for 19 hours, then concentrated to ⅓ volume, diluted with water (30 mL) and acidified to pH 4-5 with 1N HCl. The resulting precipitate was collected by filtration, washed with water and Et2O then dried under reduced pressure to afford (S)-5-(1-(5-fluoro-2-methoxypyridin-3-yl)-2-hydroxyethylamino)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (121 mg, 45% yield) as a white powder. MS (apci) m/z=347.9 (M+H).

Workup

  1. waitat 50° C. for 19 hours
  2. concentrationconcentrated
  3. additiondiluted with water (30 mL)
  4. filtrationThe resulting precipitate was collected by filtration
  5. washwashed with water and Et2O
  6. customthen dried under reduced pressure

Sources & evidence

ORD record
ord-954b8a45a5354b75b6150a37770b7453
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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