2-[4-(4-aminobutyl)phenoxy]-N,N-dimethylacetamide → HCID 178484633, compound

HRID 132565Notes

Reaction equation

HRID 132565 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]1[CH:18]=[CH:17][C:9]([O:10][CH2:11][C:12]([N:14]([CH3:16])[CH3:15])=[O:13])=[CH:8][CH:7]=1.I.[NH2:20][C:21]1[C:22]([C:29]([NH:31][C:32](=[NH:35])SC)=[O:30])=[N:23][C:24]([Cl:28])=[C:25]([NH2:27])[N:26]=1>C(O)C>[NH2:20][C:21]1[C:22]([C:29]([N:31]=[C:32]([NH2:35])[NH:1][CH2:2][CH2:3][CH2:4][CH2:5][C:6]2[CH:18]=[CH:17][C:9]([O:10][CH2:11][C:12]([N:14]([CH3:15])[CH3:16])=[O:13])=[CH:8][CH:7]=2)=[O:30])=[N:23][C:24]([Cl:28])=[C:25]([NH2:27])[N:26]=1

Participants

4

Reactant 2

HCID 220544312-[4-(4-aminobutyl)phenoxy]-N,N-dimethylacetamideHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 1

HCID 178484633HCID 178484633, compoundYield 28%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 2-[4-(4-aminobutyl)phenoxy]-N,N-dimethylacetamide 29 (67 mg, 0.27 mmol) in absolute ethanol (1 mL) was stirred at 65° C. for 30 min, after which 1-(3,5-diamino-6-chloropyrazine-2-carbonyl)-2-methylisothiourea hydriodide (110 mg, 0.29 mmol) was added in one portion. The reaction mixture was stirred at that temperature for 3 h and then cooled to room temperature. The reaction mixture was 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 (200:10:0, 200:10:1, v/v) to give 2-(4-{4-[N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)guanidino]butyl}-phenoxy)-N,N-dimethylacetamide as a yellow solid (35 mg, 28% yield). This solid was dissolved in methanol (2 mL) and added to 4 N aqueous HCl (4 drops). Concentration in vacuo gave 2-(4-{4-[N′-(3,5-diamino-6-chloropyrazine-2-carbonyl)-guanidino]butyl}phenoxy)-N,N-dimethylacetamide hydrochloride (30, PSA 16313). mp 130-132° C. (decomposed). 1H NMR (300 MHz, CD3OD) δ 1.69 (m, 4H), 2.60 (m, 2H), 2.95 (s, 3H), 3.10 (s, 3H), 3.35 (m, 2H), 4.75 (s, 2H), 6.80 (d, 2H), 7.10 (d, 2H). m/z (ESI): 463 [C20H27ClN8O3+H]+.

Workup

  1. concentrationThe reaction mixture was concentrated 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 (200:10:0, 200:10:1

Sources & evidence

ORD record
ord-fcc0dc37e022446cb3b0b5bb1f52a0d3
Source dataset
uspto-grants-2008_06
Patent number
US07388013B2

Reaction notes

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