Sodium Cyanide → Ethyl 6-cyano-2-methyl-5-(pentan-3-ylamino)nicotinate

HRID 906185Notes

Reaction equation

Br[C:2]1[C:12]([NH:13][CH:14]([CH2:17][CH3:18])[CH2:15][CH3:16])=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[C:4]([CH3:19])[N:3]=1.[C-:20]#[N:21].[Na+].C([Sn](Cl)(CCCC)CCCC)CCC>C(#N)C.O>[C:20]([C:2]1[C:12]([NH:13][CH:14]([CH2:17][CH3:18])[CH2:15][CH3:16])=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[C:4]([CH3:19])[N:3]=1)#[N:21]

Participants

Conditions

Temperature: 88 °C

Procedure

To a solution of ethyl 6-bromo-2-methyl-5-(pentan-3-ylamino)nicotinate (1.202 g, 3.65 mmol) in acetonitrile (30 ml) was added sodium cyanide (0.357 g, 7.3 mmol), tributyltin chloride (1.306 g, 4.015 mmol) and Pd(dpppf)3 (0.298 g, 0.365 mmol). The reaction mixture was stirred at 88° C. overnight. The reaction mixture was diluted with water (100 ml), then extracted with ethyl acetate (3×100 ml). The organic layer was washed with saturated aqueous sodium bicarbonate and brine. After evaporation of solvent, ethyl 6-cyano-2-methyl-5-(pentan-3-ylamino)nicotinate (0.59 g, 59% yield) was obtained by column chromatography. 1H NMR (400 MHz, CDCl3): 7.56 (s, 1H), 4.50 (q, J=6.8 Hz, 2H), 4.35 (br, s, 1H), 3.40 a9m, 1H), 2.64 (s, 3H), 1.80-1.50 (m, 4H), 1.42 (t, J=6.8 Hz, 3H), 1.0 (t, 6H). MS (EI) for C15H21N3O2: 276.2 (MH+).

Workup

extractionextracted with ethyl acetate (3×100 ml)
washThe organic layer was washed with saturated aqueous sodium bicarbonate and brine
customAfter evaporation of solvent

Sources & evidence

ORD record: ord-56a29621702749dba9fcb05403fd0cc4
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08012956B2

Reaction notes

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