N-methoxy-N-methyl-3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)benzamide → 3-Methyl-1-(3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)but-2-en-1-one

HRID 404810Notes

Reaction equation

HRID 404810 reaction equation
CON(C)[C:4](=[O:32])[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[CH:21][CH:20]=3)[N:15]=[CH:14][N:13]=2)[CH:6]=1.[CH3:34][C:35]([CH3:39])=[CH:36][Mg]Br>C1COCC1>[CH3:34][C:35]([CH3:39])=[CH:36][C:4]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([NH:11][C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[CH:21][CH:20]=3)[N:15]=[CH:14][N:13]=2)[CH:6]=1)=[O:32]

Participants

4

Reactant 2

HCID 57708272N-methoxy-N-methyl-3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)benzamideHCID 178448304HCID 178448304, compound

Product 1

HCID 426017403-Methyl-1-(3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)but-2-en-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of N-methoxy-N-methyl-3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)benzamide (50 mg, 0.11 mmol) in THF (0.5 mL) at 0° C. was added 2-methylpropenylmagnesium bromide (1.1 mL, 0.55 mmol, 0.5 M in THF). The reaction mixture was allowed to stir at room temperature for 30 min. It was quenched with sat. NH4Cl solution (0.5 mL) and was extracted with EtOAc (3×2 mL). The combined organic layer was washed with brine, was dried over anhydrous Na2SO4, was filtered and was concentrated under reduced pressure to give a white solid, which was further purified by column chromatography (SiO2, 60-120, chloroform/methanol, 9/1) to give 3-methyl-1-(3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)but-2-en-1-one (I-87) as an off white solid. 1H NMR (CDCl3) δ ppm: 2.01 (s, 3H), 2.20 (s, 3H), 6.14 (s, 1H), 6.71 (s, 1H), 6.95 (s, 1H), 6.99-7.02 (m, 5H), 7.11 (t, J=7.36 Hz, 1H), 7.26-7.28 (m, 2H), 7.34 (t, J=7.56 Hz, 2H), 7.40-7.53 (m, 2H), 7.65 (d, J=7 Hz, 1H), 7.86 (s, 1H), 8.32 (s, 1H); LCMS: m/e 437.2 (M+1).

Workup

  1. customIt was quenched with sat. NH4Cl solution (0.5 mL)
  2. extractionwas extracted with EtOAc (3×2 mL)
  3. washThe combined organic layer was washed with brine
  4. dry with materialwas dried over anhydrous Na2SO4
  5. filtrationwas filtered
  6. concentrationwas concentrated under reduced pressure
  7. customto give a white solid, which
  8. customwas further purified by column chromatography (SiO2, 60-120, chloroform/methanol, 9/1)

Sources & evidence

ORD record
ord-b7b9064b2a7044be9ff68aabe105a121
Source dataset
uspto-grants-2014_06
Patent number
US08748606B2

Reaction notes

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