Tetrahydrofuran → HCID 46892755, compound

HRID 1801913Notes

Reaction equation

HRID 1801913 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., 3 H) 3.92 (br. s., 3 H) 6.48 (br. s., 1 H) 7.27 (br. s., 2 H) 7.39 (br. s., 2 H) 8.07 (br. s., 2 H) 8.62 (br. s., 1 H) 10.50 (br. s., 1 H) 12.15 (br. s., 1 H) 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-2984861bba9e4306b3d1a0fde90373a9
Source dataset
uspto-grants-2013_01
Patent number
US08349851B2

Reaction notes

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