Water → HCID 18630658, compound

HRID 582568Notes

Reaction equation

HRID 582568 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C(N(CC)CC)C.[C:22]([C:24]1[CH:25]=[C:26]([N:30]=[C:31]=[O:32])[CH:27]=[CH:28][CH:29]=1)#[N:23].O>CN(C)C=O>[C:22]([C:24]1[CH:25]=[C:26]([NH:30][C:31]([NH:1][CH:2]2[CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]2)=[O:32])[CH:27]=[CH:28][CH:29]=1)#[N:23]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 27333153-Isocyanatobenzonitrile

Product 1

HCID 18630658HCID 18630658, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 4-amino-N-(t-butoxycarbonyl)piperidine (0.133 mol, 30.5 g, prepared by the method of Mach, R. H. et al., J. Med. Chem. (1993) 36(23), 3707-20) and triethylamine (1.5 equivilents, 0.2 mol, 20.2 g, 27.8 ml) in dimethylformamide (230 ml) was cooled to 0° C. and m-cyanophenylisocyanate (1.1 equivilents, 0.146 mmol, 21.1 g) in dimethylformamide (70 ml) was added dropwise. The reaction was stirred at ambient temperature for 18 h. It was poured into water and extracted with ethyl acetate (3×). The ethyl acetate extracts were washed with 1N HCl and brine, then dried (Na2SO4) and evaporated to give 43.56 g of crude material. Pure N-(3-cyanophenyl)-N'-(1-(t-butoxycarbonyl)piperidin-4-yl)urea was isolated by flash chromatography on silica gel (1.2 kg) eluted with 2:1 hexane:ethyl acetate (6 L) then 1:1 heaxane ethyl acetate collected in 800 ml fractions. Fractions 9 thru 14 contained pure product, yield 21.69 g.

Workup

  1. customprepared by the method of Mach, R
  2. extractionextracted with ethyl acetate (3×)
  3. washThe ethyl acetate extracts were washed with 1N HCl and brine
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customto give 43.56 g of crude material

Sources & evidence

ORD record
ord-295086ac30d943a6b6ff6184e5fcdf26
Source dataset
uspto-grants-1999_07
Patent number
US05925635

Reaction notes

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