[CH2:1]([C:5]1[C:13]([CH3:14])=[CH:12][C:8]([C:9](O)=[O:10])=[CH:7][N:6]=1)[CH:2]([CH3:4])[CH3:3].CC[N:17](C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.N.O1CCOCC1>CN(C=O)C>[CH2:1]([C:5]1[C:13]([CH3:14])=[CH:12][C:8]([C:9]([NH2:17])=[O:10])=[CH:7][N:6]=1)[CH:2]([CH3:4])[CH3:3]To a solution of 6-isobutyl-5-methyl-nicotinic acid (200 mg, 0.871 mmol) and DIPEA (450 mg, 3.48 mmol) in DMF (9 mL), PyBOP (498 mg, 0.958 mmol) is added at 0° C. The mixture is stirred for 15 min before 0.5 M NH3 in dioxane (6.1 mL, 3.05 mmol) is added. Stirring is continued for 2 h at rt. The mixture is concentrated to give crude 6-isobutyl-5-methyl-nicotinamide; LC-MS: tR=0.55 min, [M+1]+=193.10. This material is dissolved in DCM (8 mL), and pyridine (430 mg, 4.43 mmol) followed by trifluoroacetic anhydride (1.25 g, 5.94 mmol) is added dropwise at 0° C. The mixture is stirred at rt for 2 h before it is diluted with DCM. The mixture is washed with a 10% aq. citric acid solution followed by a sat. aq. Na2CO3-solution, dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to give 6-isobutyl-5-methyl-nicotinonitrile (126 mg) as a colourless oil; LC-MS: tR=0.90 min, [M+1]+=175.17; 1H NMR (CDCl3): δ 0.98 (d, J=6.8 Hz, 6H), 2.20 (hept. J=7 Hz, 1H), 2.38 (s, 3H), 2.74 (d, J=7.3 Hz, 2H), 7.69 (s, 1H), 8.67 (s, 1H).
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