Tetrahydrofuran → HCID 178487624, compound

HRID 1424424Notes

Reaction equation

HRID 1424424 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, 3H) 6.73 (br. s., 1H) 7.29 (m., 2H) 7.38 (m, 2H) 7.63 (br. s., 1H) 8.08 (m, 2H) 8.64 (m., 1H) 10.63 (br. s., 1H) 12.47 (br. s., 1H) 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-abd06c7ad5b5454397fe24330a68fa49
Source dataset
uspto-grants-2015_01
Patent number
US08927711B2

Reaction notes

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