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

HRID 2193615Notes

Reaction equation

HRID 2193615 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.[C:34]([Mg]Br)#[C:35][CH2:36]C>C1COCC1>[O:25]([C:22]1[CH:23]=[CH:24][C:19]([NH:18][C:16]2[N:15]=[CH:14][N:13]=[C:12]([NH:11][C:7]3[CH:6]=[C:5]([C:4](=[O:32])[C:34]#[C:35][CH3:36])[CH:10]=[CH:9][CH:8]=3)[CH:17]=2)=[CH:20][CH:21]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

4

Reactant 2

HCID 57708272N-methoxy-N-methyl-3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)benzamideHCID 178448415HCID 178448415, compound

Product 1

HCID 426017411-(3-(6-(4-Phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)but-2-yn-1-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

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 a THF solution of 1-butynylmagnesium bromide (1.1 mL, 1.1 mmol). The reaction mixture was allowed to come to rt and was stirred at rt for 30 min. The reaction mixture was quenched with saturated NH4Cl solution (0.5 mL) and was extracted with EtOAc (2×3 mL). The combined EtOAc layer was washed with brine, was dried over anhydrous Na2SO4, was filtered and was concentrated under reduced pressure to give a white solid, which h was further purified by column chromatography (SiO2, 60-120, chloroform/methanol, 9/1) to give 1-(3-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)phenyl)but-2-yn-1-one (I-88) as an off-yellow solid. NMR (DMSO-d6) δ ppm: 2.22 (s, 3H), 6.16 (s, 1H), 6.97 (d, J=8.6 Hz, 2H), 7.01 (d, J=8.8 Hz, 2H), 7.1 (t, J=7.2 Hz, 1H), 7.35-7.39 (m, 2H), 7.48 (t, J=8 Hz, 1H), 7.56 (d, J=8.8 Hz, 2H), 7.66 (d, J=7.2 Hz, 1H), 7.95 (d, J=7.6 Hz, 1H), 8.32 (s, 1H), 8.39 (s, 1H), 9.22 (s, 1H), 9.47 (s, 1H); LCMS: m/e 421.1 (M+1).

Workup

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

Sources & evidence

ORD record
ord-b3bf7aff9cd84886bf28b719f0acada5
Source dataset
uspto-grants-2012_12
Patent number
US08329901B2

Reaction notes

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