Reaction #53369

Reaction equation

3,5-Diamino-6-chloropyrazinoyl-2-methyl-pseudothiourea hydroiodide

4-(4-hydroxyphenyl)butylamine hydrobromide

4-(4-Hydroxyphenyl)butylamine hydrobromide

→

4-(4-Hydroxyphenyl)butylamidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride

Solvents

THF

triethylamine

Conditions

Workup

1. 1
   Temperatureat reflux temperature for 3 h
2. 2
   Otherthe supernatant was separated
3. 3
   Otherthe solvent was removed under reduced pressure
4. 4
   WashThe oily residue was washed with water (2×30 mL), ether (3×30 mL)
5. 5
   workup.ADDITION10% HCl (40 mL) was added
6. 6
   workup.STIRRINGThe mixture was vigorously stirred for 10 min
7. 7
   Filtrationthe yellow solid was filtered off
8. 8
   Otherdried
9. 9
   Otherrecrystallized twice from ethanol
10. 10
    Otherto give 181 mg (41%) of V as yellow solid

Procedure

1-(3,5-Diamino-6-chloropyrazinoyl-2-methyl-pseudothiourea hydroiodide (0.4 g, 1.03 mmol) was added to a suspension of 4-(4-hydroxyphenyl)butylamine hydrobromide (IV) in a mixture of THF (35 mL) and triethylamine (3 mL). The reaction mixture was stirred at reflux temperature for 3 h, then the supernatant was separated and the solvent was removed under reduced pressure. The oily residue was washed with water (2×30 mL), ether (3×30 mL) and then 10% HCl (40 mL) was added. The mixture was vigorously stirred for 10 min then the yellow solid was filtered off, dried and recrystallized twice from ethanol to give 181 mg (41%) of V as yellow solid. Purity is 98% by HPLC, retention time is 9.77 min; 1H NMR (300 MHz, DMSO-d6) δ1.56 (br s, 4H), 2.48 (br s, 2H), 3.35 (m, 2H), 6.65 (d, J=8.5 Hz, 2H), 6.95 (d, J=8.6 Hz, 2H), 7.50 (br s, 2H), 8.75 (br s, 1H), 9.05 (br .s, 1H), 9.33 (br s, 2H), 10.55 (s, 1H); 13C NMR (75 MHz, CD3OD) 28.7, 29.8, 35.4, 42.4, 111.2, 116.1, 122.0, 130.0, 134.0, 155.0, 156.1, 156.8, 157.5, 167.0; APCI MS m/z=378 [C16H20ClN7O2+H]+.

Source