Imidazole → HCID 123310675, compound

HRID 634524Notes

Reaction equation

HRID 634524 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:19]([C:21]3[O:22][C:23](=[O:37])[C:24]4[C:29]([C:30]=3[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH3:20])[N:9]=[C:10]([C:11]3[CH:16]=[C:15]([OH:17])[CH:14]=[C:13]([F:18])[CH:12]=3)[C:3]=12.N1C=CN=C1.CN(C=O)C.[CH3:48][C:49]([Si:52](Cl)([CH3:54])[CH3:53])([CH3:51])[CH3:50]>C(Cl)Cl>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:19]([C:21]3[O:22][C:23](=[O:37])[C:24]4[C:29]([C:30]=3[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)=[CH:28][CH:27]=[CH:26][CH:25]=4)[CH3:20])[N:9]=[C:10]([C:11]3[CH:12]=[C:13]([F:18])[CH:14]=[C:15]([O:17][Si:52]([C:49]([CH3:51])([CH3:50])[CH3:48])([CH3:54])[CH3:53])[CH:16]=3)[C:3]=12

Participants

6

Reactant 4

HCID 795Imidazole3×HCID 6228DimethylformamideHCID 28928tert-Butyldimethylsilyl chloride2×HCID 91809170HCID 91809170, compound

Product 1

HCID 123310675HCID 123310675, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred mixture of 3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-one (example 40, 0.20 mmol) and imidazole (40.8 mg, 0.60 mmol) in DMF (1 ml) TBDMSCl (45.2 mg, 0.30 mmol) was added at RT and the mixture was stirred for 2 hrs. Additional imidazole (16 mg) and TBDMSCl (36 mg) were added and the mixture was stirred at the same temperature for further 2 hrs. Additional imidazole (27 mg) and TBDMSCl (121 mg) were added and the stirring was continued at room temperature overnight. The reaction mixture was diluted with DCM and washed with 0.5M HCl. The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was purified by filtration on silica gel cartridge (DCM to DCM:MeOH=95:5) to afford 3-(1-(4-amino-3-(3-((tert-butyldimethylsilyl)oxy)-5-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-phenyl-1H-isochromen-1-one (intermediate Q.1, 112 mg, 0.184 mmol, 92%).

Workup

  1. additionwas added at RT
  2. stirringthe mixture was stirred at the same temperature for further 2 hrs
  3. waitthe stirring was continued at room temperature overnight
  4. washwashed with 0.5M HCl
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. filtrationThe residue was purified by filtration on silica gel cartridge (DCM to DCM:MeOH=95:5)

Sources & evidence

ORD record
ord-80c597f0148a41cb826d91151b795391
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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