4-tert-Butylbenzoyl chloride → 4-tert-butyl-N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)benzamide

HRID 1409121Notes

Reaction equation

HRID 1409121 reaction equation
[Cl:1][C:2]1[N:7]2[N:8]=[CH:9][CH:10]=[C:6]2[N:5]=[C:4]([NH2:11])[CH:3]=1.[Cl:12][C:13]1[N:18]2[N:19]=[C:20]([CH3:22])[CH:21]=[C:17]2[N:16]=[C:15]([NH2:23])[CH:14]=1.[C:24]([C:28]1[CH:36]=[CH:35][C:31]([C:32](Cl)=[O:33])=[CH:30][CH:29]=1)([CH3:27])([CH3:26])[CH3:25]>N1C=CC=CC=1>[C:24]([C:28]1[CH:29]=[CH:30][C:31]([C:32]([NH:11][C:4]2[CH:3]=[C:2]([Cl:1])[N:7]3[N:8]=[CH:9][CH:10]=[C:6]3[N:5]=2)=[O:33])=[CH:35][CH:36]=1)([CH3:27])([CH3:25])[CH3:26].[C:24]([C:28]1[CH:29]=[CH:30][C:31]([C:32]([NH:23][C:15]2[CH:14]=[C:13]([Cl:12])[N:18]3[N:19]=[C:20]([CH3:22])[CH:21]=[C:17]3[N:16]=2)=[O:33])=[CH:35][CH:36]=1)([CH3:27])([CH3:25])[CH3:26]

Participants

6

Reactant 3

HCID 743724-tert-Butylbenzoyl chlorideHCID 442513067-Chloropyrazolo[1,5-a]pyrimidin-5-amineHCID 442513077-Chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-amine

Product 2

HCID 866522564-tert-butyl-N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)benzamideYield 47%HCID 866522574-tert-butyl-N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)benzamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

7-Chloropyrazolo[1,5-a]pyrimidin-5-amine 1E (1.0 equivalent) or 7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-amine (1J, 1.0 equivalent) was dissolved in anhydrous pyridine (0.35 M). 4-t-Butylbenzoic acid chloride (1.05 equivalents) was added at 0° C., and the mixture was stirred for two hours. The reaction was then quenched with saturated NaHCO3; pyridine was removed in vacuo and the residue was extracted with EtOAc. Combined organic layers were washed twice with 0.2 N HCl to remove residual pyridine, dried over MgSO4, filtered and concentrated. Crude product was purified by column chromatography (SiO2, gradient of 15 to 30% EtOAc/hexanes). The purified product was triturated with Et2O to give 4-tert-butyl-N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)benzamide (1F, 47%) or 4-tert-butyl-N-(7-chloro-2-methylpyrazolo[1,5-a]pyrimidin-5-yl)benzamide (1K) of the product as a solid.

Workup

  1. customThe reaction was then quenched with saturated NaHCO3
  2. custompyridine was removed in vacuo
  3. extractionthe residue was extracted with EtOAc
  4. washCombined organic layers were washed twice with 0.2 N HCl
  5. customto remove residual pyridine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customCrude product was purified by column chromatography (SiO2, gradient of 15 to 30% EtOAc/hexanes)
  10. customThe purified product was triturated with Et2O

Sources & evidence

ORD record
ord-5780bfe5fa0c428184680fa3e3881b40
Source dataset
uspto-grants-2014_12
Patent number
US08921358B2

Reaction notes

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