Hydrochloric Acid → HCID 56646142, compound

HRID 1773599Notes

Reaction equation

HRID 1773599 reaction equation
Cl.C([SiH2][O:7][C:8](C)(C)[C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]2[CH:19]=[N:20][N:21]3[CH:26]=[CH:25][CH:24]=[N:23][C:22]=23)=[O:17])=[C:11]([O:27][CH3:28])[CH:10]=1)(C)(C)C.Cl[CH2:32]Cl>>[CH3:28][O:27][C:11]1[CH:10]=[C:9]([CH2:8][O:7][CH3:32])[CH:14]=[CH:13][C:12]=1[NH:15][C:16]([C:18]1[CH:19]=[N:20][N:21]2[CH:26]=[CH:25][CH:24]=[N:23][C:22]=12)=[O:17].[OH:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([C:18]2[CH:19]=[N:20][N:21]3[CH:26]=[CH:25][CH:24]=[N:23][C:22]=23)=[O:17])=[C:11]([O:27][CH3:28])[CH:10]=1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 6344DichloromethaneHCID 131734711HCID 131734711, compound

Product 2

HCID 56646142HCID 56646142, compoundHCID 56646336HCID 56646336, compound

Procedure

A solution of hydrochloric acid (1 M in Et2O, 2 mL) was added to a solution of pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [4-(tert-butyl-dimethyl-silanyloxymethyl)-2-methoxy-phenyl]-amide (160 mg, 0.388 mmol) in dichloromethane (20 mL) and the resulting mixture was stirred at room temperature for 10 minutes. A second aliquot of solution of hydrochloric acid (1 M in Et2O, 2 mL) was added and the reaction mixture was stirred for 1 hour. The resulting mixture was evaporated under reduced pressure and the yellow solid residue was washed with hexane, ethyl acetate, diethyl ether and dichloromethane. The solid and the filtrate were then combined and partitioned between dichloromethane and aqueous solution of sodium bicarbonate (5%). The organic layer was separated and the aqueous layer was extracted 3 times with dichloromethane. The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure. The yellow solid residue was purified by flash chromatography (DCM/MeOH/NH4OH) to give 80 mg of pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (2-methoxy-4-methoxymethyl-phenyl)-amide and 40 mg of pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (4-hydroxymethyl-2-methoxy-phenyl)-amide. Pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (2-methoxy-4-methoxymethyl-phenyl)-amide compound was repurified by preparative TLC (DCM/MeOH/NH4OH) and was washed with diethyl ether and hexane to give, after drying in a vacuum oven, 64 mg of as a white solid. MS=313 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred for 1 hour
  2. customThe resulting mixture was evaporated under reduced pressure
  3. washthe yellow solid residue was washed with hexane, ethyl acetate, diethyl ether and dichloromethane
  4. custompartitioned between dichloromethane and aqueous solution of sodium bicarbonate (5%)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted 3 times with dichloromethane
  7. washThe combined organic extracts were washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customThe yellow solid residue was purified by flash chromatography (DCM/MeOH/NH4OH)

Sources & evidence

ORD record
ord-bae979e8f7824d2fb6908a452daebc65
Source dataset
uspto-grants-2016_02
Patent number
US09255110B2

Reaction notes

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