Imidazole → HCID 123825481, compound

HRID 634517Notes

Reaction equation

HRID 634517 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:36])[C:24]4[C:29]([C:30]=3[C:31]3[S:35][CH:34]=[N: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.[CH3:42][C:43]([Si:46](Cl)([CH3:48])[CH3:47])([CH3:45])[CH3:44]>CN(C=O)C>[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:36])[C:24]4[C:29]([C:30]=3[C:31]3[S:35][CH:34]=[N: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:46]([C:43]([CH3:45])([CH3:44])[CH3:42])([CH3:48])[CH3:47])[CH:16]=3)[C:3]=12

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 118131051HCID 118131051, compound

Product 1

HCID 123825481HCID 123825481, compoundYield 65.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(thiazol-5-yl)-1H-isochromen-1-one (260 mg, 0.519 mmol) in dry DMF (10 ml), IMIDAZOLE (0.137 ml, 2.078 mmol) and TBDMSCl (0.270 ml, 1.558 mmol) were added and the solution stirred overnight. DMF was removed and residue was dissolved in DCM (50 mL) was washed with 0.5 N HCl aqueous solution. Organic phase was dried and solvent was removed. Crude was purified by silica gel flash chromatography (SNAP 25 g DCM:EtOH from 100:0 to 95:5) affording 3-(1-(4-amino-3-(3-((tert-butyldimethylsilyl)oxy)-5-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(thiazol-5-yl)-1H-isochromen-1-one (210 mg, 0.342 mmol, 65.8% yield) as a yellow pale solid.

Workup

  1. customDMF was removed
  2. dissolutionresidue was dissolved in DCM (50 mL)
  3. washwas washed with 0.5 N HCl aqueous solution
  4. customOrganic phase was dried
  5. customsolvent was removed
  6. customCrude was purified by silica gel flash chromatography (SNAP 25 g DCM:EtOH from 100:0 to 95:5)

Sources & evidence

ORD record
ord-4af893043d3947218a15c681467926b9
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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