Hydrochloric Acid → 5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-N-((S)-2,3-dihydroxypropoxy)pyrazolo[1,5-a]pyrimidine-3-carboxamide

HRID 1631367Notes

Reaction equation

HRID 1631367 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:19]=[CH:18][N:17]2[N:20]=[CH:21][C:22]([C:23]([NH:25][O:26][CH2:27][C@@H:28]3[CH2:32][O:31]C(C)(C)[O:29]3)=[O:24])=[C:16]2[N:15]=1.Cl>C1COCC1.C(Cl)Cl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[CH2:13][CH2:12][CH2:11][N:10]1[C:14]1[CH:19]=[CH:18][N:17]2[N:20]=[CH:21][C:22]([C:23]([NH:25][O:26][CH2:27][C@@H:28]([OH:29])[CH2:32][OH:31])=[O:24])=[C:16]2[N:15]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 866645775-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-N-(((S)-2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Product 1

HCID 867625725-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-N-((S)-2,3-dihydroxypropoxy)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-N-(((S)-2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)pyrazolo[1,5-a]pyrimidine-3-carboxamide (135 mg, 0.285 mmol) in THF (4.0 mL) was added 6M HCl (1.0 mL) dropwise and the mixture was stirred at ambient temperature for 1.5 hours. The reaction mixture was concentrated to approximately 1 mL and was diluted with H2O (5 mL). The resulting milky white mixture was extracted with EtOAc and the combined extracts were washed with 1M Na2CO3 and saturated NaCl. The EtOAc solution was dried over MgSO4 and filtered through a packed Celite pad capped with a layer of MgSO4. The solution was concentrated to give a colorless foam that was dissolved in minimal CH2Cl2 and treated with hexanes to give a white suspension. The suspension was concentrated to give the title compound as a white solid that was dried in vacuum (102 mg, 82%). MS (apci) m/z=434.0 (M+H).

Workup

  1. concentrationThe reaction mixture was concentrated to approximately 1 mL
  2. additionwas diluted with H2O (5 mL)
  3. extractionThe resulting milky white mixture was extracted with EtOAc
  4. washthe combined extracts were washed with 1M Na2CO3 and saturated NaCl
  5. dry with materialThe EtOAc solution was dried over MgSO4
  6. filtrationfiltered through a packed Celite pad
  7. customcapped with a layer of MgSO4
  8. concentrationThe solution was concentrated
  9. customto give a colorless foam that
  10. customto give a white suspension
  11. concentrationThe suspension was concentrated

Sources & evidence

ORD record
ord-bf2a84e1c6eb4adca48b2e6e17073c63
Source dataset
uspto-grants-2014_07
Patent number
US08791123B2

Reaction notes

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