4-(4-aminobutyl)phenol Hydrobromide → 4-(4-Hydroxyphenyl)butylamidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride

HRID 25091Notes

Reaction equation

HRID 25091 reaction equation
I.[NH2:2][C:3]1[C:4]([C:11]([NH:13][C:14](=[NH:17])SC)=[O:12])=[N:5][C:6]([Cl:10])=[C:7]([NH2:9])[N:8]=1.Br.[OH:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][CH2:28][CH2:29][NH2:30])=[CH:22][CH:21]=1>C1COCC1.C(N(CC)CC)C>[ClH:10].[OH:19][C:20]1[CH:21]=[CH:22][C:23]([CH2:26][CH2:27][CH2:28][CH2:29][NH:30][C:14]([NH:13][C:11]([C:4]2[C:3]([NH2:2])=[N:8][C:7]([NH2:9])=[C:6]([Cl:10])[N:5]=2)=[O:12])=[NH:17])=[CH:24][CH:25]=1

Participants

5

Reactant 2

HCID 115505224-(4-aminobutyl)phenol HydrobromideHCID 140329753methyl N-(3,5-diamino-6-chloropyrazine-2-carbonyl)carbamimidothioate;hydroiodide

Product 1

HCID 1784793374-(4-Hydroxyphenyl)butylamidino-3,5-diamino-6-chloropyrazinecarboxamide hydrochloride

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

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]+.

Workup

  1. temperatureat reflux temperature for 3 h
  2. customthe supernatant was separated
  3. customthe solvent was removed under reduced pressure
  4. washThe oily residue was washed with water (2×30 mL), ether (3×30 mL)
  5. addition10% HCl (40 mL) was added
  6. stirringThe mixture was vigorously stirred for 10 min
  7. filtrationthe yellow solid was filtered off
  8. customdried
  9. customrecrystallized twice from ethanol
  10. customto give 181 mg (41%) of V as yellow solid

Sources & evidence

ORD record
ord-e6cf1e9e452c42d2aca755bbebf4f44c
Source dataset
uspto-grants-2005_02
Patent number
US06858614B2

Reaction notes

Loading…