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

HRID 2278553Notes

Reaction equation

HRID 2278553 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.[F: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>O.CN(C=O)C.N1C=CC=CC=1>[F: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

8

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5360545SodiumHCID 162444404-Fluoro-2,3-dihydro-1H-indoleHCID 136378680[4-(2-Hydroxymethylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid

Product 1

HCID 1360984952-[2-(4-Fluoro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-(2-hydroxymethylmorpholin-4-yl)-3H-pyrimidin-4-oneYield 60%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

0.975 g of the sodium salt of (±)-[4-(2-hydroxymethylmorpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetic acid (example 25b, step 6b), 0.534 g of 4-fluoroindoline, 0.57 ml of pyridine and 15 ml of DMF are placed in a three-necked flask. 0.9 g of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride is added and the mixture is stirred at ambient temperature (20° C.) for 72 hours. The reaction mixture is poured into 50 ml of water, with stirring, and then the insoluble material is filtered off through a VF filter, and washed 3 times with approximately 15 ml of water and then with 10 ml of ethyl acetate and twice approximately 5 ml of diisopropyl ether. The solid is air-dried under a hood. 2-[2-(4-Fluoro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-(2-hydroxymethylmorpholin-4-yl)-3H-pyrimidin-4-one is isolated (0.82 g) and characterized in the form of a pinkish solid, yield 60%.

Workup

  1. stirringwith stirring
  2. filtrationthe insoluble material is filtered off through a VF
  3. filtrationfilter
  4. washwashed 3 times with approximately 15 ml of water
  5. customThe solid is air-dried under a hood

Sources & evidence

ORD record
ord-65f7a83969ac4ae58dfd6187c023f28f
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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