Dimethyl Sulfoxide → HCID 178504689, compound
Reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([F:21])([F:20])[C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=1)[N:8]=[C:7]2SC.[CH3:24][S:25]([O-:27])=[O:26].[Na+].CN(C)CCN.CS(C)=[O:37]>>[F:20][C:12]([F:21])([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=1)[C:9]1[N:8]=[C:7]([OH:37])[C:6]2[C:11](=[C:2]([S:25]([CH3:24])(=[O:27])=[O:26])[CH:3]=[CH:4][CH:5]=2)[N:10]=1Participants
Conditions
- Temperature
- 120 °C
Procedure
To a mixture of 8-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline from Example 35 step B (400 mg, 1 mmol), copper(I) trifluoromethanesulfonate benzene complex (503 mg, 1 mmol), sodium methanesulfinate (752 mg, 6.26 mmol) and N,N-dimethylethylenediamine (0.039 mL, 0.36 mmol) was added DMSO (15 mL). The reaction vessel was evacuated and flushed with argon (2×), and the mixture was heated in a microwave synthesizer at 120° C. for 10 min. The mixture was filtered and the filtrate was purified by preparative HPLC (Varian diphenyl reverse phase column, eluted with gradient of solvent B=0.05% AcOH/ACN and solvent A=5% ACN/0.05% AcOH/H2O) to afford 2-(difluoro(5-fluoropyridin-2-yl)methyl)-8-(methylsulfonyl)quinazolin-4-ol (100 mg, 27%). 1H NMR (300 MHz, DMSO-d6) δ ppm 3.22 (s, 3H) 7.81 (t, J=7.82 Hz, 1H) 8.00-8.11 (m, 2H) 8.38 (dd, J=7.54, 1.32 Hz, 1H) 8.45-8.51 (m, 1H) 8.71 (d, J=2.07 Hz, 1H) 13.64-13.78 (m, 1H).
Workup
- customThe reaction vessel was evacuated
- customflushed with argon (2×)
- filtrationThe mixture was filtered
- customthe filtrate was purified by preparative HPLC (Varian diphenyl reverse phase column
- washeluted with gradient of solvent B=0.05% AcOH/ACN and solvent A=5% ACN/0.05% AcOH/H2O)
Sources & evidence
- ORD record
- ord-4996f55bf2f648c0972095fc984f071b
- Source dataset
- uspto-grants-2014_01
- Patent number
- US08633207B2
Reaction notes
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