Triethylamine → [2-(4-{4-[N'-(3,5-Diamino-6-chloropyrazine-2-carbonyl)guanidino]butyl}phenoxy)ethyl]-carbamic acid tert-butyl ester

HRID 81322Notes

Reaction equation

HRID 81322 reaction equation
[C:1]([O:5][C:6](=[O:22])[NH:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][CH2:19][CH2:20][NH2:21])=[CH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].I.[NH2:24][C:25]1[C:26]([C:33]([NH:35][C:36](=[NH:39])SC)=[O:34])=[N:27][C:28]([Cl:32])=[C:29]([NH2:31])[N:30]=1.C(N(CC)CC)C>C1COCC1>[C:1]([O:5][C:6](=[O:22])[NH:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][CH2:19][CH2:20][NH:21][C:36]([NH2:39])=[N:35][C:33]([C:26]2[C:25]([NH2:24])=[N:30][C:29]([NH2:31])=[C:28]([Cl:32])[N:27]=2)=[O:34])=[CH:13][CH:12]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 22566154{2-[4-(4-Aminobutyl)phenoxy]ethyl}carbamic acid tert-butyl esterHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 1

HCID 178453722[2-(4-{4-[N'-(3,5-Diamino-6-chloropyrazine-2-carbonyl)guanidino]butyl}phenoxy)ethyl]-carbamic acid tert-butyl esterYield 92.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

{2-[4-(4-Aminobutyl)phenoxy]ethyl}carbamic acid tert-butyl ester 2 (1.7 g, 5.5 mmol), 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (2.6 g, 6.6 mmol), and triethylamine (3.1 mL) were combined in THF (18 mL). The reaction was stirred at reflux under argon for 1.5 h. The product mixture was allowed to cool, and the solvent was evaporated. Chromatography (silica gel, methylene chloride/methanol/concentrated ammonium hydroxide, 100:10:1) afforded 2.65 g (92%) of the pure product as a yellow foamy solid. 1H NMR (300 MHz, CDCl3) δ 1.44 (s, 9H), 1.62 (m, 2H), 1.61 (m, 2H), 1.75 (br s, 2H), 2.56 (t, 2H), 2.71 (t, 2H), 3.51 (m, 2H), 3.99 (t, 2H), 5.07 (br s, 1H), 6.80 (d, 2H), 7.08 (d, 2H).

Workup

  1. temperatureat reflux under argon for 1.5 h
  2. temperatureto cool
  3. customthe solvent was evaporated

Sources & evidence

ORD record
ord-b3ba4fdb56fd4d26a0f489f6e331e680
Source dataset
uspto-grants-2014_09
Patent number
US08846688B2

Reaction notes

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