(2E)-4-(Dimethylamino)-2-butenoyl chloride → N-(6-(6-(4-phenoxyphenoxy)pyrimidin-4-ylamino)pyridin-2-yl)but-2-enamide

HRID 2193599Notes

Reaction equation

HRID 2193599 reaction equation
[O:1]([C:8]1[CH:28]=[CH:27][C:11]([O:12][C:13]2[N:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([NH2:26])[N:21]=3)[CH:14]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN([CH2:32]/[CH:33]=[CH:34]/[C:35](Cl)=[O:36])C>CN1C(=O)CCC1.ClCCl>[O:1]([C:8]1[CH:28]=[CH:27][C:11]([O:12][C:13]2[N:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]3[N:21]=[C:22]([NH:26][C:35](=[O:36])[CH:34]=[CH:33][CH3:32])[CH:23]=[CH:24][CH:25]=3)[CH:14]=2)=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 10012053(2E)-4-(Dimethylamino)-2-butenoyl chlorideHCID 57708258N2-(6-(4-phenoxyphenoxy)pyrimidin-4-yl)pyridine-2,6-diamine

Product 1

HCID 86630631N-(6-(6-(4-phenoxyphenoxy)pyrimidin-4-ylamino)pyridin-2-yl)but-2-enamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a stirred solution of N2-(6-(4-phenoxyphenoxy)pyrimidin-4-yl)pyridine-2,6-diamine (0.65 g, 1.75 mmol) in NMP (10 mL) was added dimethylaminocrotonyl chloride (1.026 g, 7 mmol) at 0° C. The reaction mixture was allowed to come to room temperature and kept at it for 1 h. It was diluted with dichloromethane (10 mL), was washed with NaHCO3 solution (2 mL) and water (2 mL), and dried over Na2SO4. The dichloromethane solution was filtered and was concentrated under reduced pressure to give a residue that was purified by column chromatography (SiO2, 60-120, chloroform/methanol, 9/1) to give (E)-4-dimethylamino)-N-(6-(6-(4-phenoxyphenoxy)pyrimidin-4-ylamino)pyridin-2-yl)but-2-enamide (I-82) as an off white solid. 1H NMR (DMSO-d6) δ ppm: 2.19 (s, 6H), 3.08 (d, J=5.52 Hz, 2H), 6.50 (d, J=15.4 Hz, 1H), 6.77 (td, J=5.92 & 15.4 Hz, 1H), 7.00-7.07 (m, 5H), 7.15 (t, J=7.36 Hz, 1H), 7.21 (dd, J=2.2 & 8.92 Hz, 2H), 7.41 (t, J=7.52 Hz, 2H), 7.68 (t, J=7.96 Hz, 1H), 7.77 (d, J=7.96 Hz, 1H), 7.95 (s, 1H), 8.35 (s, 1H), 10.20 (s, 1H), 10.40 (s, 1H); LCMS: m/e 483 (M+1).

Workup

  1. customto come to room temperature
  2. washwas washed with NaHCO3 solution (2 mL) and water (2 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationThe dichloromethane solution was filtered
  5. concentrationwas concentrated under reduced pressure
  6. customto give a residue that
  7. customwas purified by column chromatography (SiO2, 60-120, chloroform/methanol, 9/1)

Sources & evidence

ORD record
ord-f206d1ea171946c7839ab8165e95848b
Source dataset
uspto-grants-2012_12
Patent number
US08329901B2

Reaction notes

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