Hydrochloric Acid → N-(3-amidinophenyl)-N'-(4-amidinophenyl)cycloheptylurea

HRID 1059523Notes

Reaction equation

HRID 1059523 reaction equation
Cl.[C:2]([C:4]1[CH:5]=[C:6]([N:10]([CH:22]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]#[N:21])=[CH:16][CH:15]=2)=[O:12])[CH:7]=[CH:8][CH:9]=1)#[N:3].C(=O)([O-])[O-].[NH4+:33].[NH4+:34]>C(O)C>[C:2]([C:4]1[CH:5]=[C:6]([N:10]([CH:22]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[C:11]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([C:20](=[NH:34])[NH2:21])=[CH:18][CH:19]=2)=[O:12])[CH:7]=[CH:8][CH:9]=1)(=[NH:33])[NH2:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 517111Ammonium CarbonateHCID 53652841N-(3-cyanophenyl)-N'-(4-cyanophenyl)cycloheptylurea

Product 1

HCID 54193740N-(3-amidinophenyl)-N'-(4-amidinophenyl)cycloheptylurea

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Dry hydrogen chloride gas was bubbled through an ice cooled solution of N-(3-cyanophenyl)-N′-(4-cyanophenyl)cycloheptylurea (0.065 g, 0.21 mmol) in anhydrous ethanol (5 ml) under a nitrogen atmosphere for 15 min. The reaction was stoppered and allowed to warm to ambient temperature and stir overnight. The reaction was concentrated in vacuo to give a white amorphous solid. This was dissolved in anhydrous ethanol (5 ml) and ammonium carbonate (0.118 g, 1.23 mmol) was added. The reaction was stirred under a nitrogen atmosphere at ambient temperature overnight. The reaction mixture was concentrated in vacuo to give a white solid. The product was purfied by HPLC on a Vydec® C-18 column eluting with solvent mixture A (acetonitrile:water:TFA 80:20:0.3) and solvent mixture B (water:TFA 99.7:0.3) using a gradient starting with A:B at 3:97 and changing to A:B at 70:30 over 20 minutes. The major fraction was concentrated to give N-(3-amidinophenyl)-N′-(4-amidinophenyl)cycloheptylurea as a white solid (mp204-206° C.); LRMS (M+H)+ m/z 351, (M+2H)+2 m/z 176.2; HRMS calc. 351.1933, found 351.1936; 1H NMR (DMSO-d6): 9.4(bs, 2H), 9.2(broad s, 2H), 9.18 (broad s, 2H), 7.95 (broad s, 2H), 7.8-7.5(m, 6H), 7.47 (d, 2H), 3.9(bd, 4H), 1.83(m, 4H).

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customto give a white amorphous solid
  3. stirringThe reaction was stirred under a nitrogen atmosphere at ambient temperature overnight
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. customto give a white solid
  6. washeluting with solvent mixture A (acetonitrile:water:TFA 80:20:0.3) and solvent mixture B (water:TFA 99.7:0.3)
  7. customover 20 minutes
  8. concentrationThe major fraction was concentrated

Sources & evidence

ORD record
ord-4b798a15f5c04cf7824a51873a854ca8
Source dataset
uspto-grants-2003_02
Patent number
US06521614B1

Reaction notes

Loading…