Hydrochloric Acid → N-(3-amidinophenyl)-N'-(1-amidinopiperidin-4-yl)cycloheptylurea

HRID 1059528Notes

Reaction equation

HRID 1059528 reaction equation
Cl.[C:2]([C:4]1[CH:5]=[C:6]([N:10]([CH:23]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[C:11]([NH:13][CH:14]2[CH2:19][CH2:18][N:17]([C:20](=[NH:22])[NH2:21])[CH2:16][CH2:15]2)=[O:12])[CH:7]=[CH:8][CH:9]=1)#[N:3].C(=O)([O-])[O-].[NH4+:34].[NH4+]>C(O)C>[C:2]([C:4]1[CH:5]=[C:6]([N:10]([CH:23]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[C:11]([NH:13][CH:14]2[CH2:19][CH2:18][N:17]([C:20](=[NH:21])[NH2:22])[CH2:16][CH2:15]2)=[O:12])[CH:7]=[CH:8][CH:9]=1)(=[NH:34])[NH2:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 517111Ammonium CarbonateHCID 54155874N-(3-cyanophenyl)-N'-(1-amidinopiperidin-4-yl)cycloheptylurea

Product 1

HCID 18630728N-(3-amidinophenyl)-N'-(1-amidinopiperidin-4-yl)cycloheptylurea

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Dry hydrogen chloride gas was bubbled through an ice cooled solution of N-(3-cyanophenyl)-N′-(1-amidinopiperidin-4-yl)cycloheptylurea (0.03 g, 0.075 mmol) in anhydrous ethanol (5 ml) for 15 min. The reaction was stoppered, allowed to warm to ambient temperature and stirred for 24 h. The reaction was concentrated to give a viscous residue which was dissolved in anhydrous ethanol and ammonium carbonate (0.06 g, 0.63 mmol) was added. The reaction was stirred over night at ambient temperature and then concentrated in vacuo. The crude product appeared to be about 1:2 ratio of the desired product to starting material. Pure N-(3-amidinophenyl)-N′-(1-amidinopiperidin-4-yl)cycloheptylurea was isolated 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 min, to give two major fractions: N-(3-amidinophenyl)-N′-(1-amidinopiperidin-4-yl)cycloheptylurea, the desired product eluted at 13.3 minutes, (8.2 mg); LRMS (M+2H)+2 m/z 179.8; HRMS calc. 358.2355, found 358.2349; 1H NMR (DMSO-d6): 9.25(s, 2H), 9.0(s, 2H), 7.55-7.4(m, 4H), 7.32(s, 4H), 3.95(m, 3H), 3.65(m, 2H), 3.25(m, 2H), 3.07(m, 2H), 1.8-1.6(m, 8H).

Workup

  1. concentrationThe reaction was concentrated
  2. customto give a viscous residue which
  3. stirringThe reaction was stirred over night at ambient temperature
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-042bbadc7ed547dd94c71d2a99f031de
Source dataset
uspto-grants-2003_02
Patent number
US06521614B1

Reaction notes

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