Sodium → 1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride
Reaction equation
[ClH:1].Br[C:3]1C=C(NC)C(N)=C[CH:8]=1.[Na].[N:13]1([C:19]2[N:20]=[C:21](CC(O)=O)[NH:22][C:23](=O)[CH:24]=2)[CH2:18]COC[CH2:14]1>CN(C=O)C.N1C=CC=CC=1>[ClH:1].[CH3:18][N:13]([CH3:14])[CH2:19][CH2:24][CH2:23][N:22]=[C:21]=[N:20][CH2:3][CH3:8]Participants
Procedure
In a round-bottom flask, the 4-bromo-N2-methylbenzene-1,2-diamine hydrochloride prepared above (1.2 g) is placed in a mixture of DMF (10 ml) and pyridine (10 ml) with magnetic stirring, and then N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (968 mg) and then the sodium salt of (4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetic acid, obtained in stage 2 of Example 1 (1.2 g) are added. The mixture thus obtained is stirred at ambient temperature (20° C.) overnight. After evaporation of the reaction medium, glacial acetic acid (20 ml) is added and the resulting mixture is brought to reflux (90 min). The reaction medium is concentrated, and taken up in dichloromethane and water at pH 8 (2N sodium hydroxide), so as to form a solid which is filtered off and washed with dichloromethane. The solid obtained is dissolved in methanol, adsorbed onto silica (7 g) and purified by chromatography. Purification is carried out on a silica column (50 g), elution being carried out with a mixture of dichloromethane and 9/1 dichloromethane/MeOH (with CV=75 ml; gradient: 4 CV DCM; 4 CV of 0 to 16% 9/1 DCM/MeOH; 8 CV of 16 to 20% 9/1 DCM/MeOH; 1 CV of 20 to 30% 9/1 DCM/MeOH). The fractions containing the expected compound are combined and evaporated under reduced pressure. 900 mg of 2-[(6-bromo-1-methyl-1H-benzimidazol-2-yl)methyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one are isolated, the characteristics of which are the following:
Sources & evidence
- ORD record
- ord-78cfa06ce6c146f4bfb3638440cee771
- Source dataset
- uspto-grants-2013_08
- Patent number
- US08507483B2
Reaction notes
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