Tetrahydrofuran → HCID 178487624, compound

HRID 1801912Notes

Reaction equation

HRID 1801912 reaction equation
[NH:1]1[CH:5]=[CH:4][C:3]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[N:10]=[C:9]([C:19]([O:21]CC)=O)[N:8]=2)=[N:2]1.[F:24][C:25]1[CH:30]=[CH:29][C:28]([Mg]Br)=[CH:27][CH:26]=1.C1COCC1>CC(N(C)C)=O>[NH:1]1[CH:5]=[CH:4][C:3]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[N:10]=[C:9]([C:19]([C:28]3[CH:29]=[CH:30][C:25]([F:24])=[CH:26][CH:27]=3)=[O:21])[N:8]=2)=[N:2]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 178418676HCID 178418676, compound2×HCID 178470280HCID 178470280, compound

Product 1

HCID 178487624HCID 178487624, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To ethyl 4-(1H-pyrazol-3-ylamino)-7-methoxyquinazoline-2-carboxylate (30 mg, 0.10 mmol) in dry DMA (2.5 mL) cooled in a −20° C. cooling bath was added dropwise 1N 4-fluorophenylmagnesium bromide in THF (0.306 mL, 0.306 mmol). After 2 h additional 1 N 4-fluorophenyl magnesium bromide (0.050 mL) was added. After 2 h, the reaction mixture was quenched by addition of a saturated ammonium chloride solution. The solution was concentrated and H2O was added. The precipitate was washed with water and purified by preparative thin layer chromatography on silica gel eluting with 10% MeOH/DCM to give a solid (21 mg, 60%) 1H NMR (300 MHz, DMSO-d6) δ ppm 3.93 (s, 3 H) 6.73 (br. s., 1 H) 7.29 (m., 2 H) 7.38 (m, 2H) 7.63 (br. s., 1 H) 8.08 (m, 2 H) 8.64 (m., 1 H) 10.63 (br. s., 1 H) 12.47 (br. s., 1 H) LC-MS (ESI) m/z 364 (M+H)+.

Workup

  1. temperaturecooling bath
  2. customthe reaction mixture was quenched by addition of a saturated ammonium chloride solution
  3. concentrationThe solution was concentrated
  4. additionH2O was added
  5. washThe precipitate was washed with water
  6. custompurified by preparative thin layer chromatography on silica gel eluting with 10% MeOH/DCM

Sources & evidence

ORD record
ord-8a829eb92fa2405fa1a8606f09531439
Source dataset
uspto-grants-2013_01
Patent number
US08349851B2

Reaction notes

Loading…