2-Methylindoline → 2-(4-Chloro-6-methoxypyrimidin-2-yl)-1-(2-methyl-2,3-dihydroindol-1-yl)ethanone

HRID 2278543ノート

反応式

HRID 2278543 の反応式
[Na].[Cl:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([CH2:11][C:12]([OH:14])=O)[N:4]=1.[CH3:15][CH:16]1[CH2:24][C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17]1.Cl.CN(C)CCCN=C=NCC>N1C=CC=CC=1.CN(C=O)C>[Cl:2][C:3]1[CH:8]=[C:7]([O:9][CH3:10])[N:6]=[C:5]([CH2:11][C:12]([N:17]2[C:18]3[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:24][CH:16]2[CH3:15])=[O:14])[N:4]=1

参加物

7

反応物 4

HCID 233052-MethylindolineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5360545SodiumHCID 12420761(4-Chloro-6-methoxypyrimidin-2-yl)acetic acid

生成物 1

HCID 866992722-(4-Chloro-6-methoxypyrimidin-2-yl)-1-(2-methyl-2,3-dihydroindol-1-yl)ethanone

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
20 °C

実験手順

In a three-necked flask, under argon, 4 g of the sodium salt of (4-chloro-6-methoxypyrimidin-2-yl)acetic acid (example 8b, step 3b) and 2.6 g of 2-methylindoline (6872-06-6, Aldrich) are placed in 3 ml of pyridine and 60 ml of DMF. The heterogeneous solution obtained is stirred at ambient temperature (20° C.), then N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride is added and stirring is maintained for 20 hours. The reaction mixture is concentrated in a rotary evaporator under vacuum, 100 ml of water are added, extraction is carried out with 3 times approximately 50 ml of dichloromethane, washing is carried out with 50 ml of saturated NaCl solution, drying is carried out over MgSO4 and filtration is carried out through a VF filter. The compound obtained is chromatographed on silica gel (40-63 μm), elution being carried out with dichloromethane. The fractions containing the expected compound are combined and evaporated. The compound obtained is triturated from diisopropyl ether, filtration is carried out, and drying is carried out at 20° C. 2-(4-Chloro-6-methoxypyrimidin-2-yl)-1-(2-methyl-2,3-dihydroindol-1-yl)ethanone is isolated (2.6 g) in the form of a solid (yield 46%) which is used as it is in the next step.

後処理

  1. customThe heterogeneous solution obtained
  2. stirringstirring
  3. temperatureis maintained for 20 hours
  4. concentrationThe reaction mixture is concentrated in a rotary evaporator under vacuum, 100 ml of water
  5. additionare added
  6. extractionextraction
  7. washwashing
  8. customdrying
  9. filtrationis carried out over MgSO4 and filtration
  10. filtrationfilter
  11. customThe compound obtained
  12. customis chromatographed on silica gel (40-63 μm), elution
  13. additionThe fractions containing the expected compound
  14. customevaporated
  15. customThe compound obtained
  16. filtrationis triturated from diisopropyl ether, filtration
  17. customdrying
  18. customis carried out at 20° C

出典と根拠

ORDレコード
ord-a1de119fba324c28bcc3112e5f01d4ff
出典データセット
uspto-grants-2015_09
特許番号
US09133168B2

反応ノート

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