Dichloromethane → (E)-3-chloro-N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)phenyl)acrylamide

HRID 58212

反応式

HRID 58212 の反応式
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[N:14]=[CH:13][N:12]=[C:11]([N:15]([CH3:31])[C:16]([NH:18][C:19]2[C:24]([Cl:25])=[C:23]([O:26][CH3:27])[CH:22]=[C:21]([O:28][CH3:29])[C:20]=2[Cl:30])=[O:17])[CH:10]=1.C(N(CC)CC)C.[Cl:39]/[CH:40]=[CH:41]/[C:42](O)=[O:43].C(Cl)Cl.C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC>>[Cl:39]/[CH:40]=[CH:41]/[C:42]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]1[CH:10]=[C:11]([N:15]([CH3:31])[C:16]([NH:18][C:19]2[C:20]([Cl:30])=[C:21]([O:28][CH3:29])[CH:22]=[C:23]([O:26][CH3:27])[C:24]=2[Cl:25])=[O:17])[N:12]=[CH:13][N:14]=1)=[O:43]

参加物

6

反応物 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 638124trans-3-Chloroacrylic acidHCID 1180245491-(6-((2-Aminophenyl)amino)pyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylurea

生成物 1

HCID 118029313(E)-3-chloro-N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)phenyl)acrylamide収率 61%

実験手順

The title compound was synthesized following the approach outlined in Procedure 2A (Example 100), modifying step (i) to the following procedure: To a solution of 1-(6-((2-aminophenyl)amino)pyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylurea (10 mg, 0.022 mmol), triethylamine (10.9 g, 0.11 mmol), and (E)-3-chloroacrylic acid (2.76 g, 0.026 mmol) in DCM (0.4 ml, 6.22 mmol), cooled to 0° C., was added 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (0.023 ml, 0.039 mmol, 50% solution in EtOAc). The resulting mixture was stirred at room temperature for 4 h and concentrated. The remaining residue was purified by silica gel flash chromatography to obtain the title compound (7.2 mg, yield: 61%). 1H NMR (400 MHz, CDCl3) δ 3.30 (s, 3H) 3.90 (s, 6H) 6.02 (s, 1H) 6.36 (d, J=12.92 Hz, 1H) 6.49 (s, 1H) 7.21-7.33 (m, 2H) 7.36-7.50 (m, 2H) 7.75 (d, J=6.53 Hz, 1H) 7.93 (br. s., 1H) 8.41 (s, 1H) 12.50 (s, 1H); MS (ESI): 551.0 [M+H]+

後処理

  1. customThe title compound was synthesized
  2. concentrationconcentrated
  3. customThe remaining residue was purified by silica gel flash chromatography

出典と根拠

ORDレコード
ord-e766f463ff68484ea1b6713b0723299b
出典データセット
uspto-grants-2016_09
特許番号
US09434697B2

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