Triethylamine → HCID 178512399, compound

HRID 2220905Notes

Reaction equation

HRID 2220905 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[CH:22]=[CH:21][C:9]([O:10][CH2:11][C:12]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:13])=[CH:8][CH:7]=1.C(N(CC)CC)C.I.[NH2:31][C:32]1[C:33]([C:40]([NH:42][C:43](=[NH:46])SC)=[O:41])=[N:34][C:35]([Cl:39])=[C:36]([NH2:38])[N:37]=1>C(O)C>[NH2:31][C:32]1[C:33]([C:40]([N:42]=[C:43]([NH2:46])[NH:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]2[CH:22]=[CH:21][C:9]([O:10][CH2:11][C:12]([NH:14][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)=[O:13])=[CH:8][CH:7]=2)=[O:41])=[N:34][C:35]([Cl:39])=[C:36]([NH2:38])[N:37]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 220544372-[4-(4-Aminobutyl)phenoxy]-N-phenylacetamideHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 1

HCID 178512399HCID 178512399, compoundYield 67.1%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 2-[4-(4-aminobutyl)phenoxy]-N-phenylacetamide 19 (100 mg, 0.35 mmol) and triethylamine (0.14 mL, 1.00 mmol) in absolute ethanol (2 mL) was stirred at 60° C. for 30 min, after which 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methyl-isothiourea hydriodide (140 mg, 0.37 mmol) was added in one portion. The reaction mixture was stirred at that temperature for 4 h, cooled to room temperature, and concentrated by rotary evaporation. The crude residue was triturated with water and filtered. The filter cake was purified by flash silica gel column chromatography eluting with dichloromethane/methanol/concentrated ammonium hydroxide (500:10:0, 500:10:1, 200:10:1, v/v) to give 2-(4-{4-[N′-(3,5-diamino-6-chloro-pyrazine-2-carbonyl)guanidino]butyl}phenoxy)-N-phenyl acetamide (20, PSA 17482) as a yellow solid (120 mg, 67% yield). mp 168-170° C. 1H NMR (300 MHz, DMSO-d6) δ 1.55 (m, 4H), 2.55 (m, 2H), 3.16 (m, 2H), 4.65 (s, 2H), 6.60 (br s, 2H), 6.90 (d, 2H), 7.08 (m, 2H), 7.15 (d, 2H), 7.30 (m, 5H), 7.60 (d, 2H), 9.00 ( br s, 1H), 10.00 (br s, 1H). m/z (ESI): 511 [C24H27ClN8O3+H]+.

Workup

  1. concentrationconcentrated by rotary evaporation
  2. customThe crude residue was triturated with water
  3. filtrationfiltered
  4. customThe filter cake was purified by flash silica gel column chromatography
  5. washeluting with dichloromethane/methanol/concentrated ammonium hydroxide (500:10:0, 500:10:1, 200:10:1

Sources & evidence

ORD record
ord-3fcf9984ad3a4e64bf8947835b384f63
Source dataset
uspto-grants-2008_05
Patent number
US07368447B2

Reaction notes

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