Triethylamine → 2-(4-{4-[N'-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidino]butyl}-phenoxy)-N,N-bis-(2-hydroxyethyl)acetamide

HRID 2220909Notes

Reaction equation

HRID 2220909 reaction equation
I.[NH2:2][C:3]1[C:4]([C:11]([NH:13][C:14](=[NH:17])SC)=[O:12])=[N:5][C:6]([Cl:10])=[C:7]([NH2:9])[N:8]=1.[NH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]1[CH:39]=[CH:38][C:26]([O:27][CH2:28][C:29]([N:31]([CH2:35][CH2:36][OH:37])[CH2:32][CH2:33][OH:34])=[O:30])=[CH:25][CH:24]=1.C(N(CC)CC)C>C(O)C>[NH2:2][C:3]1[C:4]([C:11]([N:13]=[C:14]([NH2:17])[NH:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]2[CH:39]=[CH:38][C:26]([O:27][CH2:28][C:29]([N:31]([CH2:35][CH2:36][OH:37])[CH2:32][CH2:33][OH:34])=[O:30])=[CH:25][CH:24]=2)=[O:12])=[N:5][C:6]([Cl:10])=[C:7]([NH2:9])[N:8]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 220544472-[4-(4-Aminobutyl)phenoxy]-N,N-bis-(2-hydroxyethyl)acetamideHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 1

HCID 1785124012-(4-{4-[N'-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidino]butyl}-phenoxy)-N,N-bis-(2-hydroxyethyl)acetamideYield 64%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

1-(3,5-Diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (0.13 g, 0.33 mmol) was added to a solution of 2-[4-(4-aminobutyl)phenoxy]-N,N-bis-(2-hydroxyethyl)acetamide 26 (0.09 g, 0.3 mmol), triethylamine (0.12 mL), and ethanol (1.7 mL). The reaction mixture was stirred at 60° C. for 3 h. The solvent was evaporated in vacuo. The residue was triturated with water and then purified by flash chromatography (silica gel, 20-10:1:0-0.2 CH2Cl2/methanol/concentrated ammonium hydroxide, v/v) to provide 2-(4-{4-[N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidino]butyl}-phenoxy)-N,N-bis-(2-hydroxyethyl)acetamide 27 (0.1 g, 64%) as a yellow solid. mp 114-116° C. 1H NMR (300 MHz, CD3OD) δ 1.70 (m, 4H), 2.60 (m, 2H), 3.32 (m, 2H), 3.50 (m, 4H), 3.70 (m, 4H), 4.81 (s, 2H), 6.85 (d, 2H), 7.10 (d, 2H). m/z (ESI): 523 [C22H31ClN8O5+H]+.

Workup

  1. customThe solvent was evaporated in vacuo
  2. customThe residue was triturated with water
  3. custompurified by flash chromatography (silica gel, 20-10:1:0-0.2 CH2Cl2/methanol/concentrated ammonium hydroxide, v/v)

Sources & evidence

ORD record
ord-a1cb9a51cbc643eda6d101c31eb60140
Source dataset
uspto-grants-2008_05
Patent number
US07368447B2

Reaction notes

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