Acryloyl chloride → N-(6-(6-(4-methoxyphenoxy)pyrimidin-4-ylamino)pyridine-2-yl)acrylamide

HRID 929872Notes

Reaction equation

HRID 929872 reaction equation
[O:1]([C:3]1[CH:23]=[CH:22][C:6]([O:7][C:8]2[N:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([NH2:21])[N:16]=3)[CH:9]=2)=[CH:5][CH:4]=1)[CH3:2].[C:24](Cl)(=[O:27])[CH:25]=[CH2:26].C([O-])(O)=O.[Na+]>C1COCC1.CN1C(=O)CCC1.C(OCC)(=O)C.CCN(CC)CC>[CH3:2][O:1][C:3]1[CH:23]=[CH:22][C:6]([O:7][C:8]2[N:13]=[CH:12][N:11]=[C:10]([NH:14][C:15]3[N:16]=[C:17]([NH:21][C:24](=[O:27])[CH:25]=[CH2:26])[CH:18]=[CH:19][CH:20]=3)[CH:9]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 3

HCID 13140Acryloyl chlorideHCID 516892Sodium BicarbonateHCID 57708329N2-(6-(4-methoxylphenoxy)pyrimidin-4-yl)pyridine-2,6-diamine

Product 1

HCID 42601818N-(6-(6-(4-methoxyphenoxy)pyrimidin-4-ylamino)pyridine-2-yl)acrylamide

Reagents, catalysts & solvents 3

HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolventHCID 22156051tetrahydrofuran N-methylpyrrolidinoneSolvent

Procedure

To a stirred solution of N2-(6-(4-methoxylphenoxy)pyrimidin-4-yl)pyridine-2,6-diamine (150 mg, 0.474 mmol) in THF/NMP (1 mL/0.5 mL) was added acryloyl chloride (64 mg, 0.712 mmol) at −10° C. under N2 atmosphere. After stirring at this temperature for 30 min, the reaction was stopped and the reaction mixture was slowly added to NaHCO3 solution (10 mL). A white solid was precipitated which was isolated by filtration and was dissolved in a mixture of ethyl acetate (5 mL) and Et3N (0.5 mL). The solution was washed with water (2 mL) and brine (2 mL). Drying over Na2SO4 followed by filtration and concentration under reduced pressure afforded a yellow solid. It was further purified by column chromatography (SiO2, 60-120, chloroform/methanol, 9/1) to give N-(6-(6-(4-methoxyphenoxy)pyrimidin-4-ylamino)pyridine-2-yl)acrylamide (I-91) as an off white solid. 1H NMR (DMSO-d6) δ ppm: 3.76 (s, 3H), 5.79 (dd, J=1.84 & 10.16 Hz, 1H), 6.30 (dd, J=1.84 & 17 Hz, 1H), 6.65 (dd, J=10.12 & 16.92 Hz, 1H), 6.96-6.99 (m, 2H), 7.02 (d, J=7.88 Hz, 1H), 7.09-7.13 (m, 2H), 7.69 (t, J=7.96 Hz, 1H), 7.76 (d, J=7.44 Hz, 1H), 7.86 (s, 1H), 8.30 (d, J=0.88 Hz, 1H), 10.17 (s, 1H), 10.17 (s, 1H); LCMS: m/e 364 (M+1).

Workup

  1. customA white solid was precipitated which
  2. customwas isolated by filtration
  3. washThe solution was washed with water (2 mL) and brine (2 mL)
  4. dry with materialDrying over Na2SO4
  5. filtrationfollowed by filtration and concentration under reduced pressure
  6. customafforded a yellow solid
  7. customIt was further purified by column chromatography (SiO2, 60-120, chloroform/methanol, 9/1)

Sources & evidence

ORD record
ord-2509e0a685f74012b64cba2d286f3529
Source dataset
uspto-grants-2016_03
Patent number
US09296704B2

Reaction notes

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