Triethylamine → 4-(3-Chloro-4-methoxybenzylamino)-5-methoxycarbonyl-6-(4-hydroxypiperidin-1-yl)-2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-7-yl)pyrimidine

HRID 917637

反応式

HRID 917637 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[CH2:5][NH:6][C:7]1[C:12]([C:13]([O:15][CH3:16])=[O:14])=[C:11]([N:17]2[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19][CH2:18]2)[N:10]=[C:9](S(C)=O)[N:8]=1.[N:32]1[CH:33]=[CH:34][N:35]2[CH2:40][CH2:39][NH:38][CH2:37][C:36]=12.C(N(CC)CC)C.CN(C)C(=O)C>C(O)(=O)CC(CC(O)=O)(C(O)=O)O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][C:29]=1[O:30][CH3:31])[CH2:5][NH:6][C:7]1[C:12]([C:13]([O:15][CH3:16])=[O:14])=[C:11]([N:17]2[CH2:22][CH2:21][CH:20]([OH:23])[CH2:19][CH2:18]2)[N:10]=[C:9]([N:38]2[CH2:39][CH2:40][N:35]3[CH:34]=[CH:33][N:32]=[C:36]3[CH2:37]2)[N:8]=1

参加物

6

反応物 4

HCID 8471TriethylamineHCID 31374DimethylacetamideHCID 132470465,6,7,8-Tetrahydroimidazo(1,2-a)pyrazineHCID 178483194-(3-Chloro-4-methoxybenzylamino)-5-methoxycarbonyl-6-(4-hydroxypiperidin-1-yl)-2-methylsulfinylpyrimidine

生成物 1

HCID 178483124-(3-Chloro-4-methoxybenzylamino)-5-methoxycarbonyl-6-(4-hydroxypiperidin-1-yl)-2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-7-yl)pyrimidine

試薬・触媒・溶媒 1

HCID 311Citric Acid溶媒

反応条件

温度
110 °C

実験手順

A mixture of whole amount of 4-(3-chloro-4-methoxybenzylamino)-5-methoxycarbonyl-6-(4-hydroxypiperidin-1-yl)-2-methylsulfinylpyrimidine (prepared in the above (5)), 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine 73 mg, triethylamine 0.083 ml and N,N-dimethylacetamide 4 ml is stirred at 110° C. for 4 hours. After cooling the reaction mixture is diluted with a 10% aqueous citric acid solution and washed with ethyl acetate. The organic layer is extracted with a 10% aqueous citric acid solution. The water layer is made basic with sodium hydrogen carbonate and extracted with ethyl acetate. The ethyl acetate layer is washed, dried and concentrated in vacuo. The residue is separated with silica gel chromatography (solvent; chloroform:methanol=100:1→50:1), and then crystallized from a mixture of ethyl acetate, methanol and isopropyl ether to give 4-(3-chloro-4-methoxybenzylamino)-5-methoxycarbonyl-6-(4-hydroxypiperidin-1-yl)-2-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-7-yl)pyrimidine as a colorless crystalline powder 20 mg.

後処理

  1. temperatureAfter cooling the reaction mixture
  2. washwashed with ethyl acetate
  3. extractionThe organic layer is extracted with a 10% aqueous citric acid solution
  4. extractionextracted with ethyl acetate
  5. washThe ethyl acetate layer is washed
  6. customdried
  7. concentrationconcentrated in vacuo
  8. customThe residue is separated with silica gel chromatography (solvent; chloroform:methanol=100:1→50:1)
  9. customcrystallized from a mixture of ethyl acetate, methanol and isopropyl ether

出典と根拠

ORDレコード
ord-8fd70a3de5cf4ff98bf061d22d682787
出典データセット
uspto-grants-2007_09
特許番号
US07273868B2

関連ノート

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