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

HRID 268992Notes

Reaction equation

HRID 268992 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.C1COCC1.C1([Mg]Br)CC1.C1COCC1.[NH4+].[Cl-]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[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][CH:10]=[C:6]3[N:5]=2)=[CH:12][CH:13]=1

Participants

8

Reactant 4

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

Product 1

HCID 670009395-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidineYield 69%

Reagents, catalysts & solvents 3

HCID 66790640zinc chloride THFCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-chloro-5-(4-chloro-phenyl)-pyrazolo[1,5-a]pyrimidine (2.1 g, 8.0 mmol) and tetrakis(triphenylphosphine)palladium (0.92 g, 0.8 mmol) in THF (14 mL) was added at 20° C. 0.25 M cyclopropylzinc chloride/THF suspension (ca. 128 mL, 32 mmol; freshly prepared by stirring a mixture of 64 mL of 0.5 M cyclopropylmagnesium bromide/THF and 64 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 1.5 h. After the slow addition at 0° C. of saturated aqueous NH4Cl solution (20 mL), the mixture was partitioned between EtOAc and 10% sodium chloride solution. The organic layer was dried (Na2SO4) and evaporated in vacuo. The residue was chromatographed on silica gel using EtOAc/hexane (1:5 v/v) as eluent to give 5-(4-chloro-phenyl)-7-cyclopropyl-pyrazolo-[1,5-a]pyrimidine (1.50 g, 69%) as an off-white solid. MS (ISP) 270.4 [(M+H)+]; mp 137-138° C.

Workup

  1. customfreshly prepared
  2. temperature) and the mixture was refluxed in an atmosphere of argon for 1.5 h
  3. customthe mixture was partitioned between EtOAc and 10% sodium chloride solution
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. customevaporated in vacuo
  6. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-5f556869432f4af99967dab0b11c2742
Source dataset
uspto-grants-2008_11
Patent number
US07446113B2

Reaction notes

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