Bromotrimethylsilane → HCID 178461768, compound

HRID 1821593Notes

Reaction equation

HRID 1821593 reaction equation
C[O:2][P:3](=[O:36])([O:34]C)[O:4][C@@H:5]([CH3:33])[CH2:6][NH:7][C:8]1[N:13]=[C:12]([O:14][C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=2[F:22])[N:11]=[C:10]2[NH:23][N:24]=[C:25]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[Cl:32])[C:9]=12.C[Si](Br)(C)C>C(Cl)Cl>[Cl:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[C:25]1[C:9]2[C:10](=[N:11][C:12]([O:14][C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=3[F:22])=[N:13][C:8]=2[NH:7][CH2:6][C@@H:5]([O:4][P:3](=[O:2])([OH:34])[OH:36])[CH3:33])[NH:23][N:24]=1

Participants

4

Reactant 2

HCID 76113BromotrimethylsilaneHCID 178502991HCID 178502991, compound

Product 1

HCID 178461768HCID 178461768, compoundYield 76.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To (S)-phosphoric acid 2-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-1-methyl-ethyl ester dimethyl ester (3.1 g, 5.74 mmol) in 35 mL methylene chloride was added trimethylsilyl bromide (2.97 mL, excess) The reaction mixture was stirred for four hours at room temperature, and then solvent was removed under reduced pressure. Methanol (80 mL) was added, and the reaction mixture was stirred at room temperature. Solvent was again removed under reduced pressure, and the residue was added to 2N NaOH (100 mL) and EtOAc (mL). The mixture was stirred for 15 minutes, then the organic layer was separated, washed with saturated brine, dried over MgSO4, filtered and concentrated under reduced pressure to give 2.243 g of (S)-phosphoric acid mono-{2-[3-(2-chloro-phenyl)-6-(2,4-difluoro-phenoxy)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-1-methyl-ethyl}ester, MS (M+H)=512. This solid was converted to 2.182 g of the corresponding disodium salt by treatment with 15 Ml of 0.5M NaOCH3 in MeOH; MP>300° C., MS (M+H)=512.

Workup

  1. customsolvent was removed under reduced pressure
  2. additionMethanol (80 mL) was added
  3. stirringthe reaction mixture was stirred at room temperature
  4. customSolvent was again removed under reduced pressure
  5. additionthe residue was added to 2N NaOH (100 mL) and EtOAc (mL)
  6. stirringThe mixture was stirred for 15 minutes
  7. customthe organic layer was separated
  8. washwashed with saturated brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b573499fb6a44949817710b4fe3eae98
Source dataset
uspto-grants-2009_10
Patent number
US07608603B2

Reaction notes

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