Ammonium Chloride → Ethyl 5-(4-chloro-phenyl)-7-ethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

HRID 418164Notes

Reaction equation

HRID 418164 reaction equation
Cl[C:2]1[N:7]2[N:8]=[CH:9][CH:10]=[C:6]2[N:5]=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[CH:3]=1.[Cl-].[CH2:19]([Zn+])[CH3:20].C1[CH2:26][O:25]CC1.[CH2:27]([Mg]Cl)[CH3:28].C1C[O:34]CC1.[Cl-].[NH4+]>C1COCC1.[Cl-].[Zn+2].[Cl-].C1COCC1>[CH2:27]([C:9]1[C:10]([C:26]([OH:25])=[O:34])=[C:6]2[N:5]=[C:4]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)[CH:3]=[C:2]([CH2:19][CH3:20])[N:7]2[N:8]=1)[CH3:28]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 210357027-Chloro-5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidineHCID 178420661HCID 178420661, compoundHCID 178420662HCID 178420662, compound

Product 1

HCID 66650349Ethyl 5-(4-chloro-phenyl)-7-ethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acidYield 54%

Reagents, catalysts & solvents 2

HCID 66790640zinc chloride THFCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-chloro-5-(4-chloro-phenyl)-pyrazolo[1,5-a]pyrimidine (1.0 g, 3.0 mmol), tetrakis(triphenylphosphin)palladium (0.35 g, 0.3 mmol) in THF (5 mL) was added at 20° C. 0.4 M ethylzinc chloride/THF solution (30 mL, 12 mmol; freshly prepared by stirring a mixture of 6 mL of 2 M ethylmagnesium chloride/THF and 24 mL of 0.5 M zinc chloride/THF for 1 h at 0° C. followed by 1 h at 20° C.) and the mixture was refluxed in an atmosphere of argon for 2 h. After the slow addition at 0° C. of sat. aqueous ammonium chloride solution (8 mL), the mixture was partitioned between ethyl acetate and 10% sodium chloride solution. The organic layer was evaporated in vacuo and the residue chromatographed on silica gel using ethyl acetate/cyclo-hexane (1:4 v/v) as eluent to give ethyl 5-(4-chloro-phenyl)-7-ethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (0.53 g, 54%). This material was saponified using in an analogous manner the procedure described in example C.22, step d), to give the title compound. White solid; MS (ISN) 330.1 [(M−H)−]; mp 227° C.

Workup

  1. customfreshly prepared
  2. temperature) and the mixture was refluxed in an atmosphere of argon for 2 h
  3. customthe mixture was partitioned between ethyl acetate and 10% sodium chloride solution
  4. customThe organic layer was evaporated in vacuo
  5. customthe residue chromatographed on silica gel

Sources & evidence

ORD record
ord-1948e16a337149a5962f6b60278f040d
Source dataset
uspto-grants-2012_01
Patent number
US08093263B2

Reaction notes

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