Hydrochloric Acid → HCID 66649912, compound

HRID 419739Notes

Reaction equation

HRID 419739 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[CH:6]=[CH:5][C:4]=1[C:10]1[NH:14][C:13]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[N:26]=[CH:25][N:24]=[C:23]4[NH:27][N:28]=[CH:29][C:22]=34)[CH2:17][CH2:16]2)=[N:12][CH:11]=1>CO>[ClH:2].[Cl:2][C:3]1[CH:8]=[C:7]([Cl:9])[CH:6]=[CH:5][C:4]=1[C:10]1[NH:14][C:13]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[N:26]=[CH:25][N:24]=[C:23]4[NH:27][N:28]=[CH:29][C:22]=34)[CH2:17][CH2:16]2)=[N:12][CH:11]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 666499131H-Pyrazolo[3,4-d]pyrimidine, 4-[4-[5-(2,4-dichlorophenyl)-1H-imidazol-2-yl]-1-piperidinyl]-

Product 1

HCID 66649912HCID 66649912, compoundYield 129.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Heat a mixture of 4-(4-(2,4-dichlorophenyl)-1H-imidazol-2-yl)piperidine (270 mg, 0.91 mmol), 4-chloro-1H-pyrazolo[3,4-d]pyrimidine (280 mg, 1.82 mmol), Et3N (0.63 mL, 4.5 mmol), and 2-propanol (10 mL) at 90° C. overnight under N2. Cool the mixture to room temperature and pour into water (100 mL). Extract the mixture with CH2Cl2 (2×200 mL), combine the organic layers, and wash with water (50 mL). Dry (Na2SO4) the organic layer, filter the mixture, and concentrate the filtrate in vacuo. Purify the residue by silica gel chromatography (25 g of SiO2, elute with CH2Cl2/CMA 4:1, 1000 mL) to provide 4-(4-(5-(2,4-dichlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine (304 mg, 80%). Add hydrochloric acid (2.0 M aqueous, 0.36 mL, 0.72 mmol) to a suspension of 4-(4-(5-(2,4-dichlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine (300 mg, 0.72 mmol) in methanol (7 mL). Concentrate the mixture in vacuo to dryness. Dissolve the residue in methanol (2 mL) and add diethyl ether (50 mL) to form a precipitate. Filter the precipitate, and wash the filter cake with Et2O. Dissolve the solid in methanol (10 mL) and remove the solvent in vacuo to dryness to provide 4-(4-(5-(2,4-dichlorophenyl)-1H-imidazol-2-yl)piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine hydrochloride (210 mg, 65%) as an off-white solid.

Workup

  1. concentrationConcentrate the mixture in vacuo to dryness
  2. dissolutionDissolve the residue in methanol (2 mL)
  3. additionadd diethyl ether (50 mL)
  4. customto form a precipitate
  5. filtrationFilter the precipitate
  6. washwash the filter cake with Et2O
  7. dissolutionDissolve the solid in methanol (10 mL)
  8. customremove the solvent in vacuo to dryness

Sources & evidence

ORD record
ord-0b04ea2f6620458a969b74fe4a99ada0
Source dataset
uspto-grants-2012_01
Patent number
US08093383B2

Reaction notes

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