Triethylamine → HCID 178512399, compound

HRID 252176Notes

Reaction equation

HRID 252176 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-phenylacetamide (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-319f1cfb85654b2fa685a03bff0d5a7e
Source dataset
uspto-grants-2011_01
Patent number
US07868010B2

Reaction notes

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