Hydrochloric Acid → 4-{4-[5-(4-Fluoro-3-trifluoromethyl-phenyl)-3-methyl-1H-imidazol-2-yl]-piperidin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine

HRID 419753Notes

Reaction equation

HRID 419753 reaction equation
Cl.C(OC([N:9]1[CH2:14][CH2:13][CH:12]([C:15]2[N:16]([CH3:31])[CH:17]=[C:18]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[C:22]([C:27]([F:30])([F:29])[F:28])[CH:21]=3)[N:19]=2)[CH2:11][CH2:10]1)=O)(C)(C)C.Cl[C:33]1[N:38]=[CH:37][N:36]=[C:35]2[NH:39][N:40]=[CH:41][C:34]=12.C(N(CC)CC)C>ClCCl>[F:26][C:23]1[CH:24]=[CH:25][C:20]([C:18]2[NH:19][CH:15]([CH:12]3[CH2:11][CH2:10][N:9]([C:33]4[N:38]=[CH:37][N:36]=[C:35]5[NH:39][N:40]=[CH:41][C:34]=45)[CH2:14][CH2:13]3)[N:16]([CH3:31])[CH:17]=2)=[CH:21][C:22]=1[C:27]([F:29])([F:28])[F:30]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 2210954-Chloro-1H-pyrazolo[3,4-d]pyrimidineHCID 666499314-[4-(4-Fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 666500374-{4-[5-(4-Fluoro-3-trifluoromethyl-phenyl)-3-methyl-1H-imidazol-2-yl]-piperidin-1-yl}-1H-pyrazolo[3,4-d]pyrimidineYield 92.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add hydrogen chloride (4.00 equiv; 81.41 mmoles; 20.35 mL) to a solution of 4-[4-(4-Fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (8.7 g; 1.00 equiv; 20.35 mmoles) in dichloromethane (101.77 mL), at room temperature. Stir the solution at room temperature for 1 hour. Remove the solvent under reduced pressure, and dissolve the crude in isopropyl alcohol (101.77 mL). Add 4-chloro-1H-pyrazolo[3,4-d]pyrimidine (1.65 equiv; 33.58 mmoles; 5.19 g) and triethylamine (10 equiv; 203.54 mmoles; 28.37 mL). Stir the mixture at reflux for 1 hour. Remove the solvent under reduced pressure and triturate the crude in water overnight. Filter the solid and triturated in hot acetonitrile, filter and dry in vacuo. 4-{4-[5-(4-Fluoro-3-trifluoromethyl-phenyl)-3-methyl-1H-imidazol-2-yl]-piperidin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine (8.42 g; 18.86 mmoles; 92.66% yield) is obtained as a light yellow solid.

Workup

  1. customat room temperature
  2. customRemove the solvent under reduced pressure
  3. dissolutiondissolve the crude in isopropyl alcohol (101.77 mL)
  4. stirringStir the mixture
  5. temperatureat reflux for 1 hour
  6. customRemove the solvent under reduced pressure
  7. customtriturate the crude in water overnight
  8. filtrationFilter the solid
  9. customtriturated in hot acetonitrile
  10. filtrationfilter
  11. customdry in vacuo

Sources & evidence

ORD record
ord-f06a42cbc7b64fe58610fa18fe458a0a
Source dataset
uspto-grants-2012_01
Patent number
US08093383B2

Reaction notes

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