Lithium hydroxide, monohydrate → (R)-5-(2-(2-(2-(tert-butoxycarbonylamino)ethylamino)-5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

HRID 1426922Notes

Reaction equation

HRID 1426922 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][NH:11][C:12]1[C:17]([C@H:18]2[CH2:22][CH2:21][CH2:20][N:19]2[C:23]2[CH:28]=[CH:27][N:26]3[N:29]=[CH:30][C:31]([C:32]([O:34]CC)=[O:33])=[C:25]3[N:24]=2)=[CH:16][C:15]([F:37])=[CH:14][N:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[Li].O>C1COCC1.CO.O>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][NH:11][C:12]1[C:17]([C@H:18]2[CH2:22][CH2:21][CH2:20][N:19]2[C:23]2[CH:28]=[CH:27][N:26]3[N:29]=[CH:30][C:31]([C:32]([OH:34])=[O:33])=[C:25]3[N:24]=2)=[CH:16][C:15]([F:37])=[CH:14][N:13]=1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86691721(R)-ethyl 5-(2-(2-(2-(tert-butoxycarbonylamino)ethylamino)-5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate

Product 1

HCID 86691722(R)-5-(2-(2-(2-(tert-butoxycarbonylamino)ethylamino)-5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (R)-ethyl 5-(2-(2-(2-(tert-butoxycarbonylamino)ethylamino)-5-fluoropyridin-3-yl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine-3-carboxylate (38 mg, 0.074 mmol) in THF/MeOH/water (2:2:1, 0.7 mL) was added LiOH—H2O (9.3 mg, 0.22 mmol), followed by stirring at 50° C. for 18 hours. After removal of solvent, the reaction residue was taken up in water (0.5 mL), and acidified with 1 N HCl (0.22 mL) to pH 3. The reaction mixture was extracted with EtOAc (3×2 mL), dried (Na2SO4), filtered and concentrated to give the desired product, which was used in the next step directly without further purification, assuming quantitative conversion. MS (apci) m/z=486.0 (M+H).

Workup

  1. customAfter removal of solvent
  2. extractionThe reaction mixture was extracted with EtOAc (3×2 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7f64d78da36c44618c111f7f11981eed
Source dataset
uspto-grants-2015_01
Patent number
US08933084B2

Reaction notes

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