Isopropanol → 1H-Pyrazolo[3,4-d]pyrimidine, 4-[4-[5-(2,4-dichlorophenyl)-1H-imidazol-2-yl]-1-piperidinyl]-

HRID 419738Notes

Reaction equation

HRID 419738 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]([CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[NH:12][CH:13]=1.Cl[C:21]1[N:26]=[CH:25][N:24]=[C:23]2[NH:27][N:28]=[CH:29][C:22]=12.CCN(CC)CC.CC(O)C>O>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:10][C:11]([CH:14]2[CH2:19][CH2:18][N:17]([C:21]3[N:26]=[CH:25][N:24]=[C:23]4[NH:27][N:28]=[CH:29][C:22]=34)[CH2:16][CH2:15]2)=[N:12][CH:13]=1

Participants

6

Reactant 4

HCID 3776IsopropanolHCID 8471TriethylamineHCID 2210954-Chloro-1H-pyrazolo[3,4-d]pyrimidineHCID 178477954HCID 178477954, compound

Product 1

HCID 666499131H-Pyrazolo[3,4-d]pyrimidine, 4-[4-[5-(2,4-dichlorophenyl)-1H-imidazol-2-yl]-1-piperidinyl]-Yield 80.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

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. temperatureHeat
  2. extractionExtract the mixture with CH2Cl2 (2×200 mL)
  3. washwash with water (50 mL)
  4. dry with materialDry (Na2SO4) the organic layer
  5. filtrationfilter the mixture
  6. concentrationconcentrate the filtrate in vacuo
  7. customPurify the residue
  8. washby silica gel chromatography (25 g of SiO2, elute with CH2Cl2/CMA 4:1, 1000 mL)

Sources & evidence

ORD record
ord-1b336130d8664aaca994fbec865a81aa
Source dataset
uspto-grants-2012_01
Patent number
US08093383B2

Reaction notes

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