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

HRID 582567Notes

Reaction equation

HRID 582567 reaction equation
Cl.[C:2]([C:4]1[CH:5]=[C:6]([N:10]([CH:27]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:11]([NH:13][CH:14]2[CH2:19][CH2:18][N:17]([CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:16][CH2:15]2)=[O:12])[CH:7]=[CH:8][CH:9]=1)#[N:3].C(=O)([O-])[O-].[NH4+:38].[NH4+]>C(O)C>[C:2]([C:4]1[CH:5]=[C:6]([N:10]([CH:27]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]2)[C:11]([NH:13][CH:14]2[CH2:19][CH2:18][N:17]([CH2:20][C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:16][CH2:15]2)=[O:12])[CH:7]=[CH:8][CH:9]=1)(=[NH:38])[NH2:3]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 517111Ammonium CarbonateHCID 53879433N-(3-Cyanophenyl)-N'-(1-benzylpiperidin-4-yl)cycloheptylurea

Product 1

HCID 54137994N-(3-amidinophenyl)-N'-(1-benzylpiperidin-4-yl)cycloheptylurea

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Dry hydrogen chloride gas was bubbled through an ice cooled solution of N-(3-cyanophenyl)-N'-(1-benzylpiperidin-4-yl)cycloheptylurea (0.03 g, 0.077 mmol) in anhydrous ethanol (10 ml) under a nitrogen atmosphere for 15 min. The reaction was stoppered, allowed to warm to ambient temperature and stirred for 24 h. The reaction was concentrated to a solid and dissolved in anhydrous ethanol (5 ml) and ammonium carbonate (0.023 g, 0.23 mmol) was added. The reaction mixture was stirred at ambient temperature overnight then was concentrated in vacuo. N-(3-Amidinophenyl)-N'-(1-benzylpiperidin-4-yl)cycloheptylurea was purified 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 15 min. The major fraction eluting at 15 minutes was concentrated to give N-(3-amidinophenyl)-N'-(1-benzylpiperidin-4-yl)cycloheptylurea as an amorphous solid; LRMS (M+H)+ m/z 406, (M+2H)+2 m/z 203.8; 1H NMR (DMSO-d6): 9.52(broad s, 1H), 9.27(s, 2H), 9.02(s, 2H), 7.5(m, 9H), 4.3(m,m, 2H), 3.95(m, 1H), 3.67(m, 2H), 3.42(m, 2H), 3.2(m, 2H), 3.1(m, 2H), 2.05-1.6(m, 8H).

Workup

  1. concentrationThe reaction was concentrated to a solid
  2. dissolutiondissolved in anhydrous ethanol (5 ml)
  3. stirringThe reaction mixture was stirred at ambient temperature overnight
  4. concentrationthen was concentrated in vacuo
  5. customN-(3-Amidinophenyl)-N'-(1-benzylpiperidin-4-yl)cycloheptylurea was purified by HPLC on a Vydec® C-18 column
  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 15 min
  8. washThe major fraction eluting at 15 minutes
  9. concentrationwas concentrated

Sources & evidence

ORD record
ord-435ef4eab7b94bcc822337cb4c11f143
Source dataset
uspto-grants-1999_07
Patent number
US05925635

Reaction notes

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