Potassium trimethylsilanolate → N-(7-(2-Fluoro-4-iodophenylamino)-8-fluoro-4-methylquinazolin-6-yl)cyclopropanesulfonamide
Reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:21]2[C:12](=[CH:13][C:14]3[C:15]([CH3:23])=[N:16][CH:17]=[N:18][C:19]=3[C:20]=2[F:22])[N:11]([S:24]([CH:27]2[CH2:29][CH2:28]2)(=[O:26])=[O:25])C1=O.C[Si](C)(C)[O-].[K+]>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:21]1[C:20]([F:22])=[C:19]2[C:14]([C:15]([CH3:23])=[N:16][CH:17]=[N:18]2)=[CH:13][C:12]=1[NH:11][S:24]([CH:27]1[CH2:28][CH2:29]1)(=[O:25])=[O:26]Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 3-(2-fluoro-4-iodophenyl)-1-(cyclopropylsulfonyl)-4-fluoro-8-methyl-1H-imidazo[4,5-g]quinazolin-2(3H)-one (46 mg, 0.09 mmol) in THF (5 ml) was added potassium trimethylsilanolate (35 mg, 0.27 mmol). The reaction was stirred at room temperature for 16 h, quenched with saturated aqueous NH4Cl solution (5 ml), and extracted with EtOAc (2×10 ml). The combined organic solution was washed with brine (15 ml), dried over MgSO4, and concentrated. Silica gel chromatography (EtOAc:Hexanes=50:50) yielded 39 mg (90%) of the title compound as a light yellow solid. m/z=515 [M−1]−. 1H NMR (DMSO-d6, 400 MHz): δ 0.85 (m, 4H), 2.75 (m, 1H), 2.87 (s, 3H), 6.61 (m, 1H), 7.36 (d, J=8 Hz, 1H), 7.67 (d, J=11 Hz, 1H), 8.02 (s, 2H), 9.07 (s, 1H), 9.78 (s, 1H).
Workup
- customquenched with saturated aqueous NH4Cl solution (5 ml)
- extractionextracted with EtOAc (2×10 ml)
- washThe combined organic solution was washed with brine (15 ml)
- dry with materialdried over MgSO4
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-fbbb9939e0ce46989491bafad2bf35fd
- Source dataset
- uspto-grants-2010_10
- Patent number
- US07820664B2
Reaction notes
Loading…