Sodium Carbonate → {4-[3-({2-[(3,5-Diamino-6-chloro-pyrazine-2-carbonyl)-amino]-ethyl}-methyl-amino)-propyl]-phenoxy}-acetic acid methyl ester

HRID 882912Notes

Reaction equation

HRID 882912 reaction equation
[CH3:1][NH:2][CH2:3][CH2:4][NH:5][C:6]([C:8]1[C:13]([NH2:14])=[N:12][C:11]([NH2:15])=[C:10]([Cl:16])[N:9]=1)=[O:7].[CH3:17][O:18][C:19](=[O:32])[CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][CH2:30]Br)=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Na+].[Na+]>CC(C)=O>[CH3:17][O:18][C:19](=[O:32])[CH2:20][O:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][CH2:30][N:2]([CH2:3][CH2:4][NH:5][C:6]([C:8]2[C:13]([NH2:14])=[N:12][C:11]([NH2:15])=[C:10]([Cl:16])[N:9]=2)=[O:7])[CH3:1])=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 198618223,5-diamino-6-chloro-N-(2-methylaminoethyl)pyrazine-2-carboxamide2×HCID 67028183[4-(3-Bromo-propyl)-phenoxy]-acetic acid methyl ester2×

Product 1

HCID 86656655{4-[3-({2-[(3,5-Diamino-6-chloro-pyrazine-2-carbonyl)-amino]-ethyl}-methyl-amino)-propyl]-phenoxy}-acetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid (2-methylamino-ethyl)-amide (Intermediate E) (0.97 g, 2.7 mmol) and [4-(3-Bromo-propyl)-phenoxy]-acetic acid methyl ester (Intermediate Q) (2.33 g, 8.12 mmol) in acetone (30 mL) is added sodium carbonate (0.86 g, 8.12 mmol), and the reaction is heated at reflux for 4 days. After this time, the reaction is allowed to cool to RT, filtered, and concentrated in vacuo. The residue is purified by reverse phase chromatography (Isolute™ C18, 0-100% acetonitrile in water with 0.1% TFA) to yield {4-[3-({2-[(3,5-Diamino-6-chloro-pyrazine-2-carbonyl)-amino]-ethyl}-methyl-amino)-propyl]-phenoxy}-acetic acid methyl ester. [M+H]+ 451.

Workup

  1. temperaturethe reaction is heated
  2. temperatureat reflux for 4 days
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by reverse phase chromatography (Isolute™ C18, 0-100% acetonitrile in water with 0.1% TFA)

Sources & evidence

ORD record
ord-78323c4a3d3244da9b2c825fe48775c3
Source dataset
uspto-grants-2012_08
Patent number
US08236808B2

Reaction notes

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