alpha-Naphthyl isocyanate → N-{4-[1-(Naphthylaminocarbonyl)-piperidin-4-yl]-butyl}-3-(pyridin-3-yl)-propionamide

HRID 1178405Notes

Reaction equation

[C:1]1([N:11]=[C:12]=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[NH:14]1[CH2:19][CH2:18][CH:17]([CH2:20][CH2:21][CH2:22][CH2:23][NH:24][C:25](=[O:34])[CH2:26][CH2:27][C:28]2[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=2)[CH2:16][CH2:15]1>C1COCC1>[C:1]1([NH:11][C:12]([N:14]2[CH2:19][CH2:18][CH:17]([CH2:20][CH2:21][CH2:22][CH2:23][NH:24][C:25](=[O:34])[CH2:26][CH2:27][C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)[CH2:16][CH2:15]2)=[O:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1

Participants

Conditions

Temperature: 0 °C

Procedure

2.6 ml (17.7 mmol) 1-naphthyl isocyanate are dissolved in 15 ml absolute THF and cooled to ca. 0° C. under moisture exclusion. 5.1 g (17.7 mmol) N-(4-piperidin-4-yl -butyl)-3-(pyridin-3-yl)-propionamide are dissolved in 35 ml absolute THF and added dropwise under ice cooling. The mixture is stirred at RT overnight without further cooling. Subsequently, the solvent is drawn off under vacuum to a large extent and the residue is chromatographically pre-purified over silica gel with CHCl3/CH3OH (90/10) and further purified by flash-chromatography with CHCl3/CH3OH (95/5 to 90/10). After drawing off the solvent, this is crystallized from isopropanol/diisopropyl ether. Colorless crystals with an MP of 143-144° C.; yield 0.77 g (9%).

Workup

additionadded dropwise under ice cooling
customthe residue is chromatographically pre-purified over silica gel with CHCl3/CH3OH (90/10)
customfurther purified by flash-chromatography with CHCl3/CH3OH (95/5 to 90/10)
customthis is crystallized from isopropanol/diisopropyl ether

Sources & evidence

ORD record: ord-f2228ae4be5e4a808dcf6159d4b09036
Source dataset: uspto-grants-2007_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07276524B2

Reaction notes

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