Bromotrimethylsilane → HCID 58009045, compound

HRID 2368830Notes

Reaction equation

HRID 2368830 reaction equation
[P:1]([O:44]CC)([O:41]CC)([O:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[N:17][C:18]=3[NH2:20])[N:13]([CH2:21][C:22]3[N:23]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[CH3:40])[C:24](=[O:33])[C:25]4[C:30]([CH:31]=3)=[CH:29][CH:28]=[CH:27][C:26]=4[CH3:32])[N:12]=2)[CH:5]=1)=[O:2].C[Si](Br)(C)C>CC#N>[P:1]([OH:41])([OH:44])([O:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[C:6]([C:11]2[C:19]3[C:14](=[N:15][CH:16]=[N:17][C:18]=3[NH2:20])[N:13]([CH2:21][C:22]3[N:23]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[CH3:40])[C:24](=[O:33])[C:25]4[C:30]([CH:31]=3)=[CH:29][CH:28]=[CH:27][C:26]=4[CH3:32])[N:12]=2)[CH:5]=1)=[O:2]

Participants

4

Reactant 2

HCID 76113Bromotrimethylsilane2×HCID 58008960HCID 58008960, compound

Product 1

HCID 58009045HCID 58009045, compoundYield 91.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

3-(4-Amino-1-((8-methyl-1-oxo-2-o-tolyl-1,2-dihydroisoquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-5-fluorophenyl diethyl phosphate 4302 (170 mg, 0.26 mmol) was dissolved in anhydrous CH3CN (5 mL) and cooled to 0° C. under an argon atmosphere. TMSBr (0.34 mL, 2.64 mmol) was slowly added via a syringe and the resulting mixture was stirred from 0° C. to RT for 16 h. LC-MS showed small amount of starting material left, additional amount of TMSBr (0.1 mL) was added and stirred at RT for 5 h. LC-MS showed the complete conversion. The mixture was concentrated in vacuo, and the residue was dissolved in Et2O (10 mL) and H2O (0.5 mL) and stirred for 30 min. The mixture was concentrated in vacuo to affords the desired product, 3-(4-amino-1-((8-methyl-1-oxo-2-o-tolyl-1,2-dihydroisoquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-5-fluorophenyl dihydrogen phosphate 4903 (140 mg, 91% yield).

Workup

  1. waitleft
  2. stirringstirred at RT for 5 h
  3. concentrationThe mixture was concentrated in vacuo
  4. dissolutionthe residue was dissolved in Et2O (10 mL)
  5. stirringH2O (0.5 mL) and stirred for 30 min
  6. concentrationThe mixture was concentrated in vacuo

Sources & evidence

ORD record
ord-da1f9112381b42d0be1ea02b69a687fc
Source dataset
uspto-grants-2014_04
Patent number
US08703777B2

Reaction notes

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