Chlorotrimethylsilane → HCID 178497302, compound

HRID 1801937Notes

Reaction equation

HRID 1801937 reaction equation
[C:1]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]=1[NH:14][C:15](=O)[C:16]([F:25])([F:24])[C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)(=[O:3])[NH2:2].C(N(CC)CC)C.C[Si](Cl)(C)C>ClCCCl>[F:24][C:16]([F:25])([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[C:15]1[N:2]=[C:1]([OH:3])[C:4]2[C:5](=[CH:6][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:12][CH:13]=2)[N:14]=1

Participants

5

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 8471TriethylamineHCID 66611125HCID 66611125, compound

Product 1

HCID 178497302HCID 178497302, compoundYield 90.2%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of methyl 4-carbamoyl-3-(2,2-difluoro-2-(4-fluorophenyl)acetamido)benzoate (1.3 g, 3.5 mmol) in DCE (20 mL) were added triethylamine (20 mL, 142 mmol) and trimethylsilyl chloride (6.7 mL, 53.2 mmol and the mixture was heated 85° C. overnight. The mixture was allowed to cool to rt, and then was concentrated under reduced pressure. The residue was partitioned between EtOAc (150 mL) and H2O (100 mL), and the separated aqueous phase was extracted with EtOAc (3×150 mL). The combined organic layers were washed with brine (100 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was treated with MeOH with sonication, and the solid was collected by filtration to afford methyl 2-(difluoro(4-fluorophenyl)methyl)-4-hydroxyquinazoline-7-carboxylate (1.1 g, 89%). 1H NMR (300 MHz, DMSO-d6) δ 3.91 (s, 3H), 7.39 (t, 2H), 7.78 (t, 2H), 8.06 (d, 1H), 8.16 (s, 1H), 8.27 (d, 1H), 13.34 (s, 1H); LC-MS (ESI) m/z 349 (M+H)−.

Workup

  1. temperatureto cool to rt
  2. concentrationwas concentrated under reduced pressure
  3. customThe residue was partitioned between EtOAc (150 mL) and H2O (100 mL)
  4. extractionthe separated aqueous phase was extracted with EtOAc (3×150 mL)
  5. washThe combined organic layers were washed with brine (100 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. additionThe residue was treated with MeOH with sonication
  10. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-e8a935242be74cc7a91b1d873c9ecfc0
Source dataset
uspto-grants-2013_01
Patent number
US08349851B2

Reaction notes

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