1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-(4-Chloro-6-methoxypyrimidin-2-yl)-1-(3,3-dimethyl-2,3-dihydroindol-1-yl)ethanone

HRID 2278541Notes

Reaction equation

HRID 2278541 reaction equation
[Na].[CH3:2][O:3][C:4]1[CH:9]=[C:8]([Cl:10])[N:7]=[C:6]([CH2:11][C:12]([OH:14])=O)[N:5]=1.[CH3:15][C:16]1([CH3:25])[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[NH:18][CH2:17]1.CN(C)CCCN=C=NCC>CN(C)C=O.N1C=CC=CC=1>[Cl:10][C:8]1[CH:9]=[C:4]([O:3][CH3:2])[N:5]=[C:6]([CH2:11][C:12]([N:18]2[C:19]3[C:24](=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:16]([CH3:25])([CH3:15])[CH2:17]2)=[O:14])[N:7]=1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 5360545SodiumHCID 118049123,3-DimethylindolineHCID 12420761(4-Chloro-6-methoxypyrimidin-2-yl)acetic acid

Product 1

HCID 866992712-(4-Chloro-6-methoxypyrimidin-2-yl)-1-(3,3-dimethyl-2,3-dihydroindol-1-yl)ethanoneYield 41%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

0.5 g of the sodium salt of (4-methoxy-6-chloropyrimidin-2-yl)acetic acid (example 8b, step 3b), 0.33 g of 3,3-dimethyl-2,3-dihydro-1H-indole (CAS 1914-02-9), 0.4 ml of pyridine and 5 ml of dimethylformamide are placed in a three-necked flask so as to obtain a homogeneous brown solution. 512 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide are added at ambient temperature and the mixture is stirred at ambient temperature for 20 hours. The resulting product is concentrated in a rotary evaporator under vacuum, 40 ml of water are added, extraction is carried out with 3 times approximately 25 ml of dichloromethane, washing is carried out with 50 ml of saturated NaCl solution, drying is carried out over MgSO4, and the resulting product is filtered through a VF filter. The compound obtained is purified by chromatography on silica gel (40-63 μm), elution being carried out with a 98/2 dichloromethane/methanol mixture. The fractions containing the expected compound are combined and evaporated under reduced pressure. 2-(4-Chloro-6-methoxypyrimidin-2-yl)-1-(3,3-dimethyl-2,3-dihydroindol-1-yl)ethanone is isolated: 0.3 g of a yellow oil; yield 41%, which is used as it is in the next step.

Workup

  1. customso as to obtain a homogeneous brown solution
  2. concentrationThe resulting product is concentrated in a rotary evaporator under vacuum, 40 ml of water
  3. additionare added
  4. extractionextraction
  5. washwashing
  6. customdrying
  7. filtrationthe resulting product is filtered through a VF
  8. filtrationfilter
  9. customThe compound obtained
  10. customis purified by chromatography on silica gel (40-63 μm), elution
  11. additionThe fractions containing the expected compound
  12. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-60b10f4784804bf59e3e717dac6cd14a
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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