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

HRID 1668873Notes

Reaction equation

HRID 1668873 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-058630f219e247659732c5df015d220c
Source dataset
uspto-grants-2011_08
Patent number
US07989465B2

Reaction notes

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