Tetrahydrofuran → HCID 46892755, compound

HRID 625766Notes

Reaction equation

HRID 625766 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C:7]([NH:18][C:19]3[CH:23]=[C:22]([CH3:24])[NH:21][N:20]=3)=[N:8][C:9]([C:13]([O:15]CC)=O)=[N:10]2)=[CH:5][CH:4]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([Mg]Br)=[CH:28][CH:27]=1.C1COCC1>CC(N(C)C)=O>[F:25][C:26]1[CH:31]=[CH:30][C:29]([C:13]([C:9]2[N:8]=[C:7]([NH:18][C:19]3[CH:23]=[C:22]([CH3:24])[NH:21][N:20]=3)[C:6]3[C:11](=[CH:12][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[N:10]=2)=[O:15])=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 66614015HCID 66614015, compoundHCID 178418676HCID 178418676, compound

Product 1

HCID 46892755HCID 46892755, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To ethyl 7-methoxy-4-(5-methyl-1H-pyrazol-3-ylamino)quinazoline-2-carboxylate (379 mg, 1.16 mmol) in dry DMA (16 mL) cooled in a −30° C. bath was added dropwise 1N 4-fluorophenylmagnesium bromide in THF (4.05 mL, 4.05 mmol). After 4 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 diethyl ether to give a yellow solid (415 mg, 95%). 1H NMR (300 MHz, DMSO-d6) δ ppm 2.18 (br. s., 3H) 3.92 (br. s., 3H) 6.48 (br. s., 1H) 7.27 (br. s., 2H) 7.39 (br. s., 2H) 8.07 (br. s., 2H) 8.62 (br. s., 1H) 10.50 (br. s., 1H) 12.15 (br. s., 1H) LC-MS (ESI) m/z 378 (M+H)+.

Workup

  1. customAfter 4 h the reaction mixture was quenched by addition of a saturated ammonium chloride solution
  2. concentrationThe solution was concentrated
  3. additionH2O was added
  4. washThe precipitate was washed with water and diethyl ether

Sources & evidence

ORD record
ord-c5bfd2ef899c4d1e8eeebf134d650b24
Source dataset
uspto-grants-2016_04
Patent number
US09308207B2

Reaction notes

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