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

HRID 418166Notes

Reaction equation

HRID 418166 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-].[CH:19]1([Zn+])[CH2:21][CH2:20]1.C1[CH2:27][O:26]CC1.C1([Mg]Br)CC1.C1C[O:36]CC1.[Cl-].[NH4+]>C1COCC1.[Cl-].[Zn+2].[Cl-].C1COCC1>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([C:4]2[CH:3]=[C:2]([CH:19]3[CH2:21][CH2:20]3)[N:7]3[N:8]=[CH:9][C:10]([C:27]([OH:26])=[O:36])=[C:6]3[N:5]=2)=[CH:12][CH:13]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 210357027-Chloro-5-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidineHCID 178420628HCID 178420628, compoundHCID 178420684HCID 178420684, compound

Product 1

HCID 666504695-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

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 (4.0 g, 12.0 mmol), tetrakis(triphenylphosphin)palladium (1.15 g, 1.0 mmol) in THF (20 mL) was added at 20° C. 0.25 M cyclopropylzinc chloride/THF suspension (ca.192 mL, 48 mol; freshly prepared by stirring a mixture of 96 mL of 0.5 M cyclopropylmagnesium bromide/THF and 96 mL of 0.5 M zinc chloride/THF (96 mL) for 1 h at 0° C. followed by 1 h at 20° C.) and the mixture was refluxed in an atmosphere of argon for 2.5 h. After the slow addition at 0° C. of sat. aqueous ammonium chloride solution (30 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/cyclohexane (1:4 v/v) as eluent to give after crystallization from ethyl acetate ethyl 5-(4-chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (2.54 g, 62%) as an off-white solid, mp 141-143° C. This material was saponified using in an analogous manner the procedure described in example C.22, step d), to give the title compound. Off-white solid, MS (ISN) 312.3 [(M−H)−]; mp 242-243° C.

Workup

  1. customfreshly prepared
  2. temperature) and the mixture was refluxed in an atmosphere of argon for 2.5 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
  6. customto give
  7. customafter crystallization from ethyl acetate ethyl 5-(4-chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (2.54 g, 62%) as an off-white solid, mp 141-143° C

Sources & evidence

ORD record
ord-52aad924eadc4f05bfa2a5129086e74e
Source dataset
uspto-grants-2012_01
Patent number
US08093263B2

Reaction notes

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