Dichloromethane → (Z)-N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)phenyl)but-2-enamide

HRID 58214

反応式

HRID 58214 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.[C:39](O)(=[O:43])/[CH:40]=[CH:41]\[CH3:42].C(Cl)Cl.C(P1(=O)OP(=O)(CCC)OP(=O)(CCC)O1)CC>>[Cl:25][C:24]1[C:23]([O:26][CH3:27])=[CH:22][C:21]([O:28][CH3:29])=[C:20]([Cl:30])[C:19]=1[NH:18][C:16](=[O:17])[N:15]([C:11]1[N:12]=[CH:13][N:14]=[C:9]([NH:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[NH:1][C:39](=[O:43])/[CH:40]=[CH:41]\[CH3:42])[CH:10]=1)[CH3:31]

参加物

6

反応物 5

HCID 6344DichloromethaneHCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 643792Isocrotonic acidHCID 1180245491-(6-((2-Aminophenyl)amino)pyrimidin-4-yl)-3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylurea

生成物 1

HCID 118029139(Z)-N-(2-((6-(3-(2,6-dichloro-3,5-dimethoxyphenyl)-1-methylureido)pyrimidin-4-yl)amino)phenyl)but-2-enamide収率 37.2%

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 (20 mg, 0.043 mmol), triethylamine (21.8 g, 0.22 mmol), and (Z)-but-2-enoic acid (4.5 g, 0.052 mmol) in DCM (0.86 ml, 13.3 mmol) was added a solution of 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (49.4 g, 0.78 mmol, 50% solution EtOAc) at 0° C., and the resulting mixture was stirred at room temperature for 2 h. The mixture was concentrated and the residue was purified by silica gel column to obtain the title compound (8.5 mg, yield: 37%). 1H NMR (400 MHz, CDCl3) δ 2.20 (dd, J=7.28, 1.76 Hz, 3H) 3.30 (s, 3H) 3.92 (s, 6H) 5.85 (dd, J=11.42, 1.76 Hz, 1H) 5.99 (s, 1H) 6.29 (dd, J=11.36, 7.34 Hz, 1H) 6.52 (s, 1H) 7.23-7.34 (m, 2H) 7.46 (d, J=7.40 Hz, 1H) 7.55 (br. s., 1H) 7.78 (d, J=7.53 Hz, 1H) 8.40 (d, J=0.88 Hz, 1H) 12.50 (s, 1H); MS (ESI): 531.3 [M+H]+.

後処理

  1. customThe title compound was synthesized
  2. concentrationThe mixture was concentrated
  3. customthe residue was purified by silica gel column

出典と根拠

ORDレコード
ord-f94e1c78f85b414a88b61521f13960c6
出典データセット
uspto-grants-2016_09
特許番号
US09434697B2

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