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 2194479Notes

Reaction equation

HRID 2194479 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 RT. Stir the solution at RT 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 triturate 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 RT
  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. customtriturate in hot acetonitrile
  10. filtrationfilter
  11. customdry in vacuo

Sources & evidence

ORD record
ord-477636b0b0254597bdf648b4b36461a5
Source dataset
uspto-grants-2012_12
Patent number
US08334293B2

Reaction notes

Loading…