Dimethyl Sulfoxide → HCID 178504655, compound

HRID 473191Notes

Reaction equation

HRID 473191 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6](SC)=[N:7][C:8]([C:12]([F:21])([F:20])[C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][N:14]=3)=[N:9]2)=[CH:4][CH:3]=1.[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:8]1[N:7]=[C:6]([OH:37])[C:5]2[C:10](=[CH:11][C:2]([S:25]([CH3:24])(=[O:27])=[O:26])=[CH:3][CH:4]=2)[N:9]=1

Participants

5

Reactant 4

HCID 679Dimethyl SulfoxideHCID 66053N,N-DimethylethylenediamineHCID 2733271Sodium methanesulfinateHCID 66609624HCID 66609624, compound

Product 1

HCID 178504655HCID 178504655, compoundYield 42%

Conditions

Temperature
130 °C

Procedure

To a mixture of 7-bromo-2-(difluoro(5-fluoropyridin-2-yl)methyl)-4-(methylthio)quinazoline from Example 7 step C (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×). The mixture was then heated in a microwave synthesizer at 130° 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)-7-(methylsulfonyl)quinazolin-4-ol (155 mg, 42%). 1H NMR (300 MHz, DMSO-d6) δ ppm 7.98-8.13 (m, 3H) 8.19 (s, 1H) 8.40 (d, J=8.29 Hz, 1H) 8.68 (d, J=2.45 Hz, 1H) 13.50 (br s, 1H).

Workup

  1. customThe reaction vessel was evacuated
  2. customflushed with argon (2×)
  3. filtrationThe mixture was filtered
  4. customthe filtrate was purified by preparative HPLC (Varian diphenyl reverse phase column
  5. washeluted with gradient of solvent B=0.05% AcOH/ACN and solvent A=5% ACN/0.05% AcOH/H2O)

Sources & evidence

ORD record
ord-b716b50980f64f2ba6b5d50a3b4590b5
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

Loading…