Ammonium Chloride → (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amine

HRID 1893762Notes

Reaction equation

HRID 1893762 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]([N+:23]([O-])=O)=[C:16]2[N:15]=1.CO.C(Cl)Cl.[NH4+].[Cl-]>C(Cl)Cl.[Zn]>[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]([NH2:23])=[C:16]2[N:15]=1

Participants

6

Reactant 3

HCID 25517Ammonium Chloride2×HCID 21226129Dichloromethane methanolHCID 673298195-[(2R)-2-(2,5-Difluorophenyl)-1-pyrrolidinyl]-3-nitropyrazolo[1,5-a]pyrimidine

Product 1

HCID 58386314(R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidin-3-amineYield 99%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 6344DichloromethaneSolvent

Procedure

To a yellowish solution of (R)-5-(2-(2,5-difluorophenyl)pyrrolidin-1-yl)-3-nitropyrazolo[1,5-a]pyrimidine (2.3 g, 6.66 mmol), in a 1:1 mixture of MeOH/DCM (30 mL/30 mL) was added Zn dust (4.36 g, 66.6 mmol) [<10 micron, Aldrich] while stirring. Saturated NH4Cl aqueous solution (30 mL) was added drop-wise to this suspension with rapid stirring. After NH4Cl addition was complete, the reaction mixture was allowed to cool to ambient temperature and stirred for another 15 minutes. The reaction was diluted with DCM (50 mL) and filtered through a GF/F paper, rinsing the wet cake with DCM. The organic layer of the filtrate was separated, and the aqueous layer was extracted with DCM (2×50 mL). The organic layers were combined, washed with brine (100 mL), dried over Na2SO4, and concentrated, to provide the basically pure product as a brownish foamy solid (2.08 g, 99% yield), which was used without further purification.

Workup

  1. stirringstirred for another 15 minutes
  2. filtrationfiltered through a GF/F paper
  3. washrinsing the wet cake with DCM
  4. customThe organic layer of the filtrate was separated
  5. extractionthe aqueous layer was extracted with DCM (2×50 mL)
  6. washwashed with brine (100 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-9b797fe429654295ae621d69bf1e765c
Source dataset
uspto-grants-2013_08
Patent number
US08513263B2

Reaction notes

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