Hydrochloric Acid → HCID 178507866, compound

HRID 529761Notes

Reaction equation

HRID 529761 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:34][CH:35]([F:37])[F:36])=[C:6]([C:8]2[N:12](COCC[Si](C)(C)C)[N:11]=[CH:10][C:9]=2[NH:21][C:22]([C:24]2[CH:25]=[N:26][N:27]3[CH:32]=[CH:31][C:30]([NH2:33])=[N:29][C:28]=23)=[O:23])[CH:7]=1.Cl>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:34][CH:35]([F:37])[F:36])=[C:6]([C:8]2[C:9]([NH:21][C:22]([C:24]3[CH:25]=[N:26][N:27]4[CH:32]=[CH:31][C:30]([NH2:33])=[N:29][C:28]=34)=[O:23])=[CH:10][NH:11][N:12]=2)[CH:7]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 1317356235-amino-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [5-(5-chloro-2-difluoromethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-amide

Product 1

HCID 178507866HCID 178507866, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of 5-amino-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [5-(5-chloro-2-difluoromethoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-amide (720 mg, 1.31 mmol) in methanol (20 mL) was treated with concentrated aqueous HCl (3 mL) and the mixture heated at 80° C. for 1 hour. The solvent was evaporated and the residue azeotroped with methanol (×3). The resultant solid was triturated with ethyl acetate, collected by filtration, washed with ethyl acetate and diethyl ether and left to air dry. The residual solid was purified by flash chromatography on silica eluting with 0-12% 2M NH3/MeOH in DCM. Collecting appropriate fractions, followed by evaporation gave 5-amino-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid [3-(5-chloro-2-difluoromethoxy-phenyl)-1H-pyrazol-4-yl]-amide as a brown solid (378 mg, 69%). LCMS (Method 4) [M+H]+=419.9, RT=2.93

Workup

  1. customThe solvent was evaporated
  2. customthe residue azeotroped with methanol (×3)
  3. customThe resultant solid was triturated with ethyl acetate
  4. filtrationcollected by filtration
  5. washwashed with ethyl acetate and diethyl ether
  6. waitleft to air
  7. customdry
  8. customThe residual solid was purified by flash chromatography on silica eluting with 0-12% 2M NH3/MeOH in DCM
  9. customCollecting appropriate fractions
  10. customfollowed by evaporation

Sources & evidence

ORD record
ord-e01977113b60447a94be3557400b28c0
Source dataset
uspto-grants-2016_05
Patent number
US09346815B2

Reaction notes

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