1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (+)-2-[2-(4-Chloro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-(2-hydroxymethylmorpholin-4-yl)-3H-pyrimidin-4-one

HRID 2278552Notes

Reaction equation

HRID 2278552 reaction equation
[Na].[OH:2][CH2:3][CH:4]1[O:9][CH2:8][CH2:7][N:6]([C:10]2[N:11]=[C:12]([CH2:17][C:18]([OH:20])=O)[NH:13][C:14](=[O:16])[CH:15]=2)[CH2:5]1.[Cl:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:23]=1[CH2:24][CH2:25][NH:26]2.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.N1C=CC=CC=1>[Cl:21][C:22]1[CH:30]=[CH:29][CH:28]=[C:27]2[C:23]=1[CH2:24][CH2:25][N:26]2[C:18](=[O:20])[CH2:17][C:12]1[NH:13][C:14](=[O:16])[CH:15]=[C:10]([N:6]2[CH2:7][CH2:8][O:9][CH:4]([CH2:3][OH:2])[CH2:5]2)[N:11]=1

Participants

7

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 30163064-ChloroindolineHCID 5360545SodiumHCID 136378680[4-(2-Hydroxymethylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid

Product 1

HCID 136098494(+)-2-[2-(4-Chloro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-(2-hydroxymethylmorpholin-4-yl)-3H-pyrimidin-4-oneYield 31%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

In a 25 ml round-bottomed flask, 42 mg of the sodium salt of [4-(2-hydroxymethylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid (example 25b, step 9b) and 22 mg of 4-chloro-2,3-dihydro-1H-indole are placed in 1 ml of dimethylformamide and 0.2 ml of pyridine, and then 33 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are added. The reaction medium is stirred at ambient temperature for 20 h, then evaporated, water is added, and the resulting mixture is triturated. The solid formed is filtered off, and rinsed successively with water, then with diisopropyl ether, with methylene chloride and then with pentane. The resulting solid is dried under vacuum for 2 h. (+)-2-[2-(4-Chloro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-(2-hydroxymethylmorpholin-4-yl)-3H-pyrimidin-4-one is isolated (18 mg) in the form of a pulverulent solid (yield=31%).

Workup

  1. customevaporated
  2. additionwater is added
  3. customthe resulting mixture is triturated
  4. customThe solid formed
  5. filtrationis filtered off
  6. washrinsed successively with water
  7. dry with materialThe resulting solid is dried under vacuum for 2 h. (+)-2-[2-(4-Chloro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-(2-hydroxymethylmorpholin-4-yl)-3H-pyrimidin-4-one

Sources & evidence

ORD record
ord-4d550acfc8a04010b407f4e7f274420d
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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