Isocyanate → 1-(5-Chloro-4-nitrothiophen-2-yl)-3-(1-methylpiperidin-4-yl)urea

HRID 1192277Notes

Reaction equation

HRID 1192277 reaction equation
[Cl:1][C:2]1[S:6][C:5](C(N=[N+]=[N-])=O)=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13].[CH3:15][N:16]1[CH2:21][CH2:20][CH:19]([NH2:22])[CH2:18][CH2:17]1.[N-:23]=[C:24]=[O:25]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Cl:1][C:2]1[S:6][C:5]([NH:23][C:24]([NH:22][CH:19]2[CH2:20][CH2:21][N:16]([CH3:15])[CH2:17][CH2:18]2)=[O:25])=[CH:4][C:3]=1[N+:12]([O-:14])=[O:13]

Participants

6

Reactant 3

HCID 105034IsocyanateHCID 27375314-Amino-1-methylpiperidineHCID 602075075-Chloro-4-nitrothiophene-2-carbonyl azide

Product 1

HCID 602075081-(5-Chloro-4-nitrothiophen-2-yl)-3-(1-methylpiperidin-4-yl)ureaYield 51%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-chloro-4-nitrothiophene-2-carbonyl azide (400 mg, 1.23 mmol) from above was dissolved in toluene (10 mL) and the resulting solution was refluxed for 2 hours. After this time, the reaction mixture was cooled to ambient temperature. 1-methylpiperidin-4-amine (155 mg, 1.36 mmol) was added drop-wise to the above solution. The resulting mixture was stirred at ambient temperature for 9 hours. After this time, TLC analysis showed no intermediate isocyanate remaining so the mixture was diluted with ethyl acetate and washed with water and brine. The organic layer was dried (Na2SO4), filtered and the solvent was removed to give the crude residue. The crude material was purified by silica gel chromatography using a 95:5 mixture of dichloromethane and methanol as eluent to afford the title product as a brown solid (200 mg, 51% yield). 1H NMR (400 MHz, d6-DMSO) δ: 10.03 (1H, br), 6.97 (1H, m), 6.86 (1H, s), 3.51 (1H, m), 2.88 (2H, m), 2.77 (1H, m) 2.32 (4H, m), 1.55 (2H, m), 1.23 (2H, m).

Workup

  1. temperaturethe resulting solution was refluxed for 2 hours
  2. washwashed with water and brine
  3. dry with materialThe organic layer was dried (Na2SO4)
  4. filtrationfiltered
  5. customthe solvent was removed
  6. customto give the crude residue
  7. customThe crude material was purified by silica gel chromatography
  8. additiona 95:5 mixture of dichloromethane and methanol as eluent

Sources & evidence

ORD record
ord-c6443f0a4a9d4e128c211fc8db63331a
Source dataset
uspto-grants-2014_03
Patent number
US08680139B2

Reaction notes

Loading…