Chlorotrimethylsilane → HCID 178517778, compound

HRID 473132Notes

Reaction equation

HRID 473132 reaction equation
[F:1][C:2]([F:22])([C:15]1[N:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=1)[C:3]([NH:5][C:6]1[CH:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([NH2:10])=[O:9])=O.Cl[Si](C)(C)C>ClCCCl>[F:1][C:2]([F:22])([C:15]1[N:20]=[CH:19][C:18]([F:21])=[CH:17][N:16]=1)[C:3]1[N:10]=[C:8]([OH:9])[C:7]2[C:6](=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:5]=1

Participants

4

Reactant 2

HCID 6397ChlorotrimethylsilaneHCID 66614711HCID 66614711, compound

Product 1

HCID 178517778HCID 178517778, compoundYield 69.8%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
85 °C

Procedure

To 2-(2,2-difluoro-2-(5-fluoropyrimidin-2-yl)acetamido)benzamide (230 mg, 1.03 mmol) were added 1,2-dichloroethane (8 mL), TEA (5.75 mL, 41.2 mmol) and chlorotrimethylsilane (2 mL, 15.45 mmol) and the mixture was heated at 85° C. in a sealed vessel overnight. The mixture was allowed to cool and then was concentrated under reduced pressure. The residue was diluted with EtOAc and washed with saturated aq NaHCO3 and brine. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0-12% MeOH/DCM to afford 2-(difluoro(5-fluoropyrimidin-2-yl)methyl)quinazolin-4-ol (210 mg, 69%). LC-MS (ESI) m/z 293 (M+H)+.

Workup

  1. temperatureto cool
  2. concentrationwas concentrated under reduced pressure
  3. additionThe residue was diluted with EtOAc
  4. washwashed with saturated aq NaHCO3 and brine
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 0-12% MeOH/DCM

Sources & evidence

ORD record
ord-d316af84fe7042cd995c1985e4dcb97c
Source dataset
uspto-grants-2014_01
Patent number
US08633207B2

Reaction notes

Loading…