Oxalyl chloride → (2E)-4-(Dimethylamino)-2-butenoyl chloride

HRID 1014108ノート

反応式

HRID 1014108 の反応式
Cl.[CH3:2][N:3](/[C:5](=[CH:9]\[CH3:10])/[C:6](O)=O)[CH3:4].[C:11](Cl)(=[O:15])[C:12]([Cl:14])=[O:13].[NH2:17][C:18]1[N:23]=[C:22]([NH:24][C:25]2[CH:30]=[C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)=[CH:34][CH:33]=3)[N:28]=[CH:27][N:26]=2)[CH:21]=[CH:20][CH:19]=1>CC#N.CN(C=O)C.CN1C(=O)CCC1.CCOC(C)=O>[CH3:4][N:3]([CH2:5]/[CH:9]=[CH:10]/[C:12]([Cl:14])=[O:13])[CH3:2].[CH3:2][N:3]([CH3:4])[CH2:5]/[CH:6]=[CH:12]/[C:11]([NH:17][C:18]1[CH:19]=[CH:20][CH:21]=[C:22]([NH:24][C:25]2[CH:30]=[C:29]([NH:31][C:32]3[CH:37]=[CH:36][C:35]([O:38][C:39]4[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=4)=[CH:34][CH:33]=3)[N:28]=[CH:27][N:26]=2)[N:23]=1)=[O:15]

参加物

9

反応物 3

HCID 65578Oxalyl chlorideHCID 57708269N4-(6-aminopyridin-2-yl)-N6-4-phenoxyphenylpyrimidine-4,6-diamineHCID 86630629Dimethylaminocrotonic acid hydrochloride

生成物 2

HCID 10012053(2E)-4-(Dimethylamino)-2-butenoyl chlorideHCID 42602745(E)-4-(dimethylamino)-N-(6-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)pyridine-2-yl)but-2-enamide

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide触媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
0 °C

実験手順

A solution of dimethylaminocrotonyl chloride was prepared by reaction of dimethylaminocrotonic acid hydrochloride (0.36 g, 2.16 mmol) in CH3CN (4 mL) containing DMF (1 drop) with oxalyl chloride (0.34 g, 2.70 mmol) according to the procedure in Example 15a. This acid chloride was added drop wise at 0° C. in to a stirred solution of N4-(6-aminopyridin-2-yl)-N6-4-phenoxyphenylpyrimidine-4,6-diamine (IR-11) (0.2 g, 0.54 mmol) in NMP (8 mL). The reaction was stirred at 0° C. for 1 h, was diluted with EtOAc (5 mL), and was washed with 10% NaHCO3 (2 mL), water (2 mL) and brine (2 mL). Drying over Na2SO4 followed by concentration under reduced pressure offered a residue which was further purified by column chromatography (SiO2, 60-120, chloroform/methanol, 9/1) to give (E)-4-(dimethylamino)-N-(6-(6-(4-phenoxyphenylamino)pyrimidin-4-ylamino)pyridine-2-yl)but-2-enamide (I-64) as a yellow solid. 1H NMR (DMSO-d6) δ ppm: 2.18 (s, 6H), 3.05 (d, J=5.2 Hz, 2H), 6.48 (d, J=15.2 Hz, 1H), 6.79 (d, J=6 & 15.6 Hz, 1H), 6.96-6.99 (m, 4H), 7.07-7.15 (m, 2H), 7.36 (t, J=7.6 Hz, 2H), 7.42 (s, 1H), 7.64-7.7 (m, 4H), 8.30 (s, 1H), 9.12 (s, 1H), 9.69 (s, 1H), 10.07 (s, 1H); LCMS: m/e 482.4 (M+1).

後処理

  1. washwas washed with 10% NaHCO3 (2 mL), water (2 mL) and brine (2 mL)
  2. dry with materialDrying over Na2SO4
  3. concentrationfollowed by concentration under reduced pressure
  4. customwas further purified by column chromatography (SiO2, 60-120, chloroform/methanol, 9/1)

出典と根拠

ORDレコード
ord-646a3b009501411593a2c49f4aa9d083
出典データセット
uspto-grants-2011_07
特許番号
US07982036B2

反応ノート

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