4-Methylmorpholine → {3-[2-(4-Benzyloxy-phenyl)-acetylamino]-propyl}-{2-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-amino]-ethyl}-dimethyl-ammonium bromide

HRID 882894Notes

Reaction equation

HRID 882894 reaction equation
[Br-:1].[NH2:2][CH2:3][CH2:4][CH2:5][N+:6]([CH2:9][CH2:10][NH:11][C:12]([C:14]1[C:19]([NH2:20])=[N:18][C:17]([NH2:21])=[C:16]([Cl:22])[N:15]=1)=[O:13])([CH3:8])[CH3:7].[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37][C:38](O)=[O:39])=[CH:33][CH:32]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.CN1CCOCC1.C1(N=C=NC2CCCCC2)CCCCC1.ON1C2C=CC=CC=2N=N1>CN(C=O)C>[Br-:1].[CH2:23]([O:30][C:31]1[CH:32]=[CH:33][C:34]([CH2:37][C:38]([NH:2][CH2:3][CH2:4][CH2:5][N+:6]([CH2:9][CH2:10][NH:11][C:12]([C:14]2[C:19]([NH2:20])=[N:18][C:17]([NH2:21])=[C:16]([Cl:22])[N:15]=2)=[O:13])([CH3:7])[CH3:8])=[O:39])=[CH:35][CH:36]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 810334-Benzyloxyphenylacetic acidHCID 86656637HCID 86656637, compound2×

Product 1

HCID 86656636{3-[2-(4-Benzyloxy-phenyl)-acetylamino]-propyl}-{2-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-amino]-ethyl}-dimethyl-ammonium bromide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of (3-amino-propyl)-{2-[(3,5-diamino-6-chloro-pyrazine-2-carbonyl)-amino]-ethyl}-dimethyl-ammonium bromide (Intermediate M) (1.0 g, 2.52 mmol), 4-benzyloxyphenylacetic acid (0.61 g, 2.52 mmol), N-methylmorpholine (1.0 mL, 9.10 mmol), N,N′-dicyclohexylcarbodiimide (0.52 g, 2.52 mmol) and 1-hydroxybenzotriazole (0.34 g, 2.52 mmol) in anhydrous DMF (20 mL) is stirred under a nitrogen atmosphere at RT for 16 h. The reaction mixture is concentrated under vacuum and is purified by column chromatography (basic alumina, 0-3% MeOH in DCM) to afford the title compound as a white solid. M+ 540. 1H NMR (400 MHz, DMSO-d6) δ 8.23 (1H, t), 8.07 (1H, t), 7.52 (2H, br), 7.41-7.28 (5H, m), 7.16 (2H, d), 7.09 (2H, br), 6.91 (2H, d), 5.05 (2H, s), 3.58-3.3.51 (2H, m), 3.40-3.25 (6H, m), 3.11-3.03 (2H, m), 3.02 (6H, s), 1.87-1.75 (2H, m).

Workup

  1. concentrationThe reaction mixture is concentrated under vacuum
  2. customis purified by column chromatography (basic alumina, 0-3% MeOH in DCM)

Sources & evidence

ORD record
ord-7e4695a8ad814d14ba788336e47c86d7
Source dataset
uspto-grants-2012_08
Patent number
US08236808B2

Reaction notes

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