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

HRID 577345ノート

反応式

HRID 577345 の反応式
[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

参加物

7

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 8471Triethylamine溶媒HCID 8857Ethyl Acetate溶媒HCID 22156051tetrahydrofuran N-methylpyrrolidinone溶媒

実験手順

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 stifling 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).

後処理

  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)

出典と根拠

ORDレコード
ord-d709a073b6c9499ebbc9791f855eba9e
出典データセット
uspto-grants-2015_05
特許番号
US09040541B2

反応ノート

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