Acetaldehyde → 2,4,6-Trifluoro-N-[6-(1-ethylpiperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide

HRID 30220Notes

Reaction equation

[F:1][C:2]1[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)=[O:14])[N:8]=1)=[O:5].[CH:27](=O)[CH3:28].C([BH3-])#N.[Na+].FC(F)(F)C(O)=O>CO>[F:26][C:21]1[CH:22]=[C:23]([F:25])[CH:24]=[C:2]([F:1])[C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([CH:15]2[CH2:16][CH2:17][N:18]([CH2:27][CH3:28])[CH2:19][CH2:20]2)=[O:14])[N:8]=1)=[O:5]

Participants

Conditions

Temperature: 90 °C

Procedure

Mix 2,4,6-trifluoro-N-[6-(piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide (26 mg), acetaldehyde (42 mg), sodium cyanoborohydride (10 mg) and trifluoroacetic acid (16.4 mg) in methanol (2 mL) in a sealed tube and heat in an oil bath at 90° C. overnight. Dilute with methanol and load on a SCX column (10 g), wash with methanol, elute the product with 2M NH3-methanol, evaporate, purify on a silica gel column (4 g, solvent: dichloromethane-2M NH3 in methanol, gradient) to obtain the title compound (8.4 mg). Mass spectrum (electrospray) m/z=392 (M+1); 1H NMR (CDCl3): 8.51 (d, 1H), 8.42 (br, 1H), 7.92 (t, 1H), 7.82 (dd, 1H), 6.84 (m, 2H), 3.63 (m, 1H), 3.02 (m, 2H), 2.44 (m, 2H), 2.04 (m, 2H), 1.87 (m, 4H), 1.60 (m, 5H), 1.11 (t, J=6.8 Hz, 3H).

Workup

washwash with methanol
washelute the product with 2M NH3-methanol
customevaporate
custompurify on a silica gel column (4 g, solvent: dichloromethane-2M NH3 in methanol, gradient)

Sources & evidence

ORD record: ord-f2c9987ab6804ea7849aecdeb559a87d
Source dataset: uspto-grants-2008_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07423050B2

Reaction notes

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