Potassium trimethylsilanolate → N-(4-fluoro-5-((4-bromo-2-chlorophenyl)amino)benzo[d]oxazol-6-yl)cyclopropanesulfonamide

HRID 928984Notes

Reaction equation

HRID 928984 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:19]3[C:11](=[CH:12][C:13]4[O:17][CH:16]=[N:15][C:14]=4[C:18]=3[F:20])[N:10]([S:21]([CH:24]3[CH2:26][CH2:25]3)(=[O:23])=[O:22])C2=O)=[C:4]([Cl:28])[CH:3]=1.C[Si](C)(C)[O-].[K+]>C1COCC1>[F:20][C:18]1[C:14]2[N:15]=[CH:16][O:17][C:13]=2[CH:12]=[C:11]([NH:10][S:21]([CH:24]2[CH2:25][CH2:26]2)(=[O:22])=[O:23])[C:19]=1[NH:8][C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=1[Cl:28]

Participants

4

Reactant 2

HCID 23668039Potassium trimethylsilanolateHCID 897053485-(4-bromo-2-chlorophenyl)-7-(cyclopropylsulfonyl)-4-fluoro-5H-imidazo[4',5':4,5]benzo[1, 2-d]oxazol-6(7H)-one

Product 1

HCID 71667809N-(4-fluoro-5-((4-bromo-2-chlorophenyl)amino)benzo[d]oxazol-6-yl)cyclopropanesulfonamideYield 63.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-(4-bromo-2-chlorophenyl)-7-(cyclopropylsulfonyl)-4-fluoro-5H-imidazo[4′,5′:4,5]benzo[1,2-d]oxazol-6(7H)-one (100 mg, 0.21 mmol) in THF (10 mL) was added potassium trimethylsilanolate (40 mg, 0.31 mmol). After stirring at room temperature for 1 h, the reaction was quenched with saturated NH4Cl (aq.). The aqueous layer was extracted with ethyl acetate (10 mL×2). The combined organic phase was washed with brine (20 mL), dried over Na2SO4, filtered and concentrated in vacuo. The residual crude product was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate, 5:1-3:1, v/v) and the product was obtained as a white solid (60 mg, 63.4% yield). 1H NMR (400 MHz, CDCl3): δ 8.10 (s, 1H), 7.97 (s, 1H), 7.40 (m, 2H), 7.31-7.26 (m, 1H), 6.81 (s, 1H), 6.40-6.36 (m, 1H), 6.23 (s, 1H), 5.86-5.72 (m, 1H), 5.25-5.13 (m, 2H), 2.85 (d, 2H), 1.30-1.22 (m, 2H), 1.15-1.20 (m, 2H). 8.17 (s, 1H), 7.97 (s, 1H), 7.49 (dd, 1H), 7.35 (s, 1H), 7.26 (dd, 1H), 6.17 (m, 1H), 5.44 (s, 1H), 2.57 (m, 1H), 1.06-1.08 (m, 2H), 1.00-1.01 (m, 2H). MS APCI (+) m/z: 461.7, [M+H].

Workup

  1. customthe reaction was quenched with saturated NH4Cl (aq.)
  2. extractionThe aqueous layer was extracted with ethyl acetate (10 mL×2)
  3. washThe combined organic phase was washed with brine (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residual crude product was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate, 5:1-3:1

Sources & evidence

ORD record
ord-c4228e07068d45c097648704d5f82621
Source dataset
uspto-grants-2016_03
Patent number
US09290468B2

Reaction notes

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