Methyl iodide → N-[2,4-Dichloro-3-(8-methyl-2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl)-phenyl]-3-trifluoromethyl-benzamide

HRID 270708ノート

反応式

HRID 270708 の反応式
[Cl:1][C:2]1[C:7]([C:8]2[C:19](=[O:20])[NH:18][C:11]3[N:12]=[C:13]([S:16][CH3:17])[N:14]=[CH:15][C:10]=3[CH:9]=2)=[C:6]([Cl:21])[CH:5]=[CH:4][C:3]=1[NH:22][C:23](=[O:34])[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=1.[H-].[Na+].I[CH3:38]>CN(C=O)C>[Cl:1][C:2]1[C:7]([C:8]2[C:19](=[O:20])[N:18]([CH3:38])[C:11]3[N:12]=[C:13]([S:16][CH3:17])[N:14]=[CH:15][C:10]=3[CH:9]=2)=[C:6]([Cl:21])[CH:5]=[CH:4][C:3]=1[NH:22][C:23](=[O:34])[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:32])([F:33])[F:31])[CH:25]=1

参加物

5

反応物 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59833903N-[2,4-Dichloro-3-(2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl)-phenyl]-3-trifluoromethyl-benzamide

生成物 1

HCID 59833840N-[2,4-Dichloro-3-(8-methyl-2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl)-phenyl]-3-trifluoromethyl-benzamide収率 98%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a solution of N-[2,4-dichloro-3-(2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl)-phenyl]-3-trifluoromethyl-benzamide (1.14 g, 2.17 mmol) in DMF (35 mL) is slowly added NaH (117.2 mg, 60%, 2.93 mmol) with stirring for 30 minutes a 0° C. Iodomethane (369 mg, 2.60 mmol) is added to above solution with stirring for 40 minutes at 0° C. The solvents are evaporated and diluted with EtOAc and washed with saturated K2CO3, brine and water. The organic layer is dried, filtered and concentrated to give crude product, which is purified by flash silica gel column, eluting with CH2Cl2 (100%) gradient to CH2Cl2/MeOH(NH3, 2N)(93/7), to give the title intermediate as a solid (1.14 g, 98.0%).

後処理

  1. stirringwith stirring for 40 minutes at 0° C
  2. customThe solvents are evaporated
  3. additiondiluted with EtOAc
  4. washwashed with saturated K2CO3, brine and water
  5. customThe organic layer is dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give crude product, which
  9. customis purified by flash silica gel column
  10. washeluting with CH2Cl2 (100%) gradient to CH2Cl2/MeOH(NH3, 2N)(93/7)

出典と根拠

ORDレコード
ord-98e79c30629d4c1199e1ad98876da7f4
出典データセット
uspto-grants-2008_11
特許番号
US07449582B2

反応ノート

読み込み中…