Pyridine → 6-(morpholin-4-yl)-2-{2-[4-(morpholin-4-yl)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}pyrimidin-4(3H)-one

HRID 2278636Notes

Reaction equation

HRID 2278636 reaction equation
N1C=CC=CC=1.[N:7]1([C:13]2[CH:21]=[CH:20][CH:19]=[C:18]3[C:14]=2[CH2:15][CH2:16][NH:17]3)[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.Cl.CN(C)CCCN=C=NCC.[N:34]1([C:40]2[N:41]=[C:42]([CH2:47][C:48]([O-])=[O:49])[NH:43][C:44](=[O:46])[CH:45]=2)[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.[Na+]>CN(C)C=O.C(OCC)(=O)C.O>[N:34]1([C:40]2[N:41]=[C:42]([CH2:47][C:48]([N:17]3[C:18]4[C:14](=[C:13]([N:7]5[CH2:8][CH2:9][O:10][CH2:11][CH2:12]5)[CH:21]=[CH:20][CH:19]=4)[CH2:15][CH2:16]3)=[O:49])[NH:43][C:44](=[O:46])[CH:45]=2)[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1

Participants

8

Reactant 4

HCID 1049PyridineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86699280HCID 86699280, compoundHCID 136041844Sodium (4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate

Product 1

HCID 1361964546-(morpholin-4-yl)-2-{2-[4-(morpholin-4-yl)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}pyrimidin-4(3H)-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

8 ml of pyridine, 200 mg of 4-morpholin-4-yl-2,3-dihydro-1H-indole (prepared using 4-bromoindoline as described in WO2007103370) and 330 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are successively added to a solution of 300 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (example 1, step 2) in 8 ml of N,N-dimethylformamide. The reaction mixture is stirred at ambient temperature for 48 hours. After the addition of 50 ml of water and extraction with ethyl acetate, the organic phases are combined and then dried over magnesium sulfate, filtered through sintered glass, and concentrated under reduced pressure. After purification of the residue by silica column chromatography, elution being carried out with a mixture of dichloromethane and 7N ammoniacal methanol (90/10), 180 mg of 6-(morpholin-4-yl)-2-{2-[4-(morpholin-4-yl)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}pyrimidin-4(3H)-one are obtained in the form of a purple powder, the characteristics of which are the following:

Workup

  1. dry with materialdried over magnesium sulfate
  2. filtrationfiltered through sintered glass
  3. concentrationconcentrated under reduced pressure
  4. customAfter purification of the residue
  5. washby silica column chromatography, elution
  6. additionbeing carried out with a mixture of dichloromethane and 7N ammoniacal methanol (90/10), 180 mg of 6-(morpholin-4-yl)-2-{2-[4-(morpholin-4-yl)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}pyrimidin-4(3H)-one
  7. customare obtained in the form of a purple powder

Sources & evidence

ORD record
ord-727627765efb4782b1911c3b89f2f840
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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