Cyanamide → HCID 11951440, compound

HRID 30154Notes

Reaction equation

HRID 30154 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]=[C:15]=[S:16])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:17]#[C:18][NH2:19].CC(C)([O-])C.[K+].Br[CH2:27][C:28]([C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=1)=[O:29]>C(O)(C)(C)C.C(#N)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([NH:14][C:15]2[S:16][C:27]([C:28](=[O:29])[C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([F:36])[CH:31]=3)=[C:18]([NH2:19])[N:17]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 9864CyanamideHCID 27374513-Fluorophenacyl bromideHCID 23665647Potassium tert-butoxideHCID 58591952Tert-butyl 4-isothiocyanatopiperidine-1-carboxylate

Product 1

HCID 11951440HCID 11951440, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6386tert-ButanolSolvent

Procedure

At 20° C., a mixture of 4-isothiocyanatopiperidine-1-carboxylic acid tert-butyl ester (2.4 g, 10 mmol) (Example 1) and cyanamide (0.42 g, 10 mmol) (Aldrich) in tert-butanol (5 mL) and acetonitrile (35 mL) was treated with potassium tert-butoxide (1.0 M/THF, 10 mL, 10 mmol, Aldrich) for 15 min. 2-bromo-1-(3-fluorophenyl)ethanone (2.0 g, 9.2 mmol)(Example 2) was added and the suspension was stirred for 2 h. Solvent was removed and the solid residue purified by silica gel chromatography (60%-70% ethyl acetate/hexane) to give 2.4 g (57% yield) of 4-[4-amino-5-(3-fluorobenzoyl)thiazol-2-ylamino]piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (DMSOd6, 300 MHz) δ1.36 (m, 2H, NCH2), 1.41 (s, 9H, 3CH3), 1.88 (m, 2H, NCH2), 2.88 (brd, 2H, NCH2), 3.6-4.0 (m, 1H, CH), 3.87 (m, 2H, NCH2), 7.31 (t, 1H, Aromatic), 7.38 (d, 1H, Aromatic), 7.48 (t, 1H, Aromatic), 7.51 (q, 1H, Aromatic), 8.01 (brd, 1H, NH), 8.48 (brd, 1H, NH), 8.48 (brd, 1H, NH), 8.70 (brd, 1H, NH).

Workup

  1. customSolvent was removed
  2. customthe solid residue purified by silica gel chromatography (60%-70% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-5e57653588dc43ecb5e27ecefe2851a2
Source dataset
uspto-grants-2008_09
Patent number
US07423053B2

Reaction notes

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