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

HRID 2278543Notes

Reaction equation

HRID 2278543 reaction equation
[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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-a1de119fba324c28bcc3112e5f01d4ff
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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