Hexamethyldisilazane → {3-[(5-biphenyl-4-yl-6-fluoro-1H-benzimidazol-2-yl)oxy]phenyl}phosphonic acid

HRID 1960137Notes

Reaction equation

HRID 1960137 reaction equation
C([O:4][P:5]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]2[NH:22][C:21]3[CH:23]=[C:24]([F:39])[C:25]([C:27]4[CH:32]=[CH:31][C:30]([C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)=[CH:29][CH:28]=4)=[CH:26][C:20]=3[N:19]=2)[CH:12]=1)(=[O:10])[O:6]C(C)C)(C)C.C[Si](N[Si](C)(C)C)(C)C.Br[Si](C)(C)C>C(Cl)Cl>[C:30]1([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)[CH:29]=[CH:28][C:27]([C:25]2[C:24]([F:39])=[CH:23][C:21]3[NH:22][C:18]([O:17][C:13]4[CH:12]=[C:11]([P:5](=[O:4])([OH:10])[OH:6])[CH:16]=[CH:15][CH:14]=4)=[N:19][C:20]=3[CH:26]=2)=[CH:32][CH:31]=1

Participants

5

Reactant 3

HCID 13838HexamethyldisilazaneHCID 76113BromotrimethylsilaneHCID 86658719[3-(5-biphenyl-4-yl-6-fluoro-1H-benzoimidazol-2-yloxy)-phenyl]-phosphonic acid diisopropyl ester

Product 1

HCID 58482531{3-[(5-biphenyl-4-yl-6-fluoro-1H-benzimidazol-2-yl)oxy]phenyl}phosphonic acid

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of compound 13-8 (40 mg, 0.073 mmol) in 3 mL of CH2Cl2 was added hexamethyldisilizane (0.3 mL), followed by bromo trimethylsilane (0.1 mL, 0.74 mmol). The reaction was allowed to stir for 18 h at ambient temperature. The organic solvent was removed in vacuo, followed by the addition of H2O (1 mL). The crude product was sonicated and yielded a white suspension. Solvent was removed in vacuo and the product was dissolved in DMSO (1.5 mL). The product was purified by prepatory HPLC using a 30-80% CH3CN with 0.05% trifluoroacetic acid gradient over 20 minutes. The pure fractions were combined and lyophilized to give the desired title compound 13-9. 1H NMR δ 7.35-7.41 (2H, m), 7.48-7.51 (3H, m), 7.56-7.66 (6H, m), 7.72-7.77 (4H, m); LC-MS: m/e 461(M+H)+.

Workup

  1. customThe organic solvent was removed in vacuo
  2. additionfollowed by the addition of H2O (1 mL)
  3. customThe crude product was sonicated
  4. customyielded a white suspension
  5. customSolvent was removed in vacuo
  6. dissolutionthe product was dissolved in DMSO (1.5 mL)
  7. customThe product was purified by prepatory HPLC
  8. waitgradient over 20 minutes

Sources & evidence

ORD record
ord-9b9bb6e2735f4bbf969342d3fd027a62
Source dataset
uspto-grants-2013_04
Patent number
US08410284B2

Reaction notes

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