Acryloyl chloride → N-methyl-N-(6-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)pyridin-2-yl)acrylamide

HRID 404793Notes

Reaction equation

HRID 404793 reaction equation
[CH3:1][NH:2][C:3]1[N:8]=[C:7]([NH:9][C:10]2[CH:15]=[C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:19][CH:18]=3)[N:13]=[CH:12][N:11]=2)[CH:6]=[CH:5][CH:4]=1.[C:30](Cl)(=[O:33])[CH:31]=[CH2:32]>CN1C(=O)CCC1.ClCCl>[CH3:1][N:2]([C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([NH:9][C:10]2[CH:15]=[C:14]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([O:23][C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)=[CH:19][CH:18]=3)[N:13]=[CH:12][N:11]=2)[N:8]=1)[C:30](=[O:33])[CH:31]=[CH2:32]

Participants

5

Reactant 2

HCID 13140Acryloyl chlorideHCID 57708271N4-(6-(methylamino)pyridine-2-yl)-N6-(4-phenoxyphenyl)pyrimidine-4,6-diamine

Product 1

HCID 42601657N-methyl-N-(6-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)pyridin-2-yl)acrylamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of N4-(6-(methylamino)pyridine-2-yl)-N6-(4-phenoxyphenyl)pyrimidine-4,6-diamine (0.07 g, 0.18 mmol) in NMP (1 mL) was added acryloyl chloride (0.032 g, 0.36 mmol) at 0° C. and the reaction mixture was stirred at rt for 1 h. The reaction mixture was diluted with dichloromethane (2 mL), was washed with NaHCO3 (1 mL), water (1 mL), and brine (1 mL). The dichloromethane solution was dried over Na2SO4 and was concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, 60-120, chloroform/methanol, 9/1) to give N-methyl-N-(6-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)pyridin-2-yl)acrylamide (I-78) as a yellow solid. 1H NMR (DMSO-d6) δ ppm: 3.22 (s, 3H), 5.60 (dd, J=2.56 & 9.76 Hz, 1H), 6.12-6.16 (m, 2H), 6.79 (d, J=7.56 Hz, 1H), 6.96 (d, J=8.64 Hz, 5H), 7.09 (t, J=7.32 Hz, 1H), 7.23 (s, 1H), 7.33-7.37 (m, 4H), 7.45 (d, J=8.2 Hz, 2H), 7.32 (t, J=7.8 Hz, 1H), 8.24 (s, 1H); LCMS: m/e 439.3 (M+1).

Workup

  1. washwas washed with NaHCO3 (1 mL), water (1 mL), and brine (1 mL)
  2. dry with materialThe dichloromethane solution was dried over Na2SO4
  3. concentrationwas concentrated under reduced pressure
  4. customThe residue was purified by column chromatography (SiO2, 60-120, chloroform/methanol, 9/1)

Sources & evidence

ORD record
ord-19bf25ca4cd74fcaaaa7ffe4e78b0fbb
Source dataset
uspto-grants-2014_06
Patent number
US08748606B2

Reaction notes

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