[CH2:1]([N:3]([CH3:14])[C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([CH3:13])[N:12]=1)[C:7](O)=O)[CH3:2].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.N1C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O>CN(C=O)C.O1CCOCC1.C(Cl)Cl>[CH2:1]([N:3]([CH3:14])[C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([CH3:13])[N:12]=1)[C:7]#[N:17])[CH3:2]To a solution of 2-(ethyl-methyl-amino)-6-methyl-isonicotinic acid (2.03 g, 8.80 mmol) and DIPEA (3.41 g, 26.4 mmol) in DMF (80 mL) is added PyBOP (5.00 g, 9.61 mmol) at 0° C. The mixture is stirred for 15 min before 0.5 M NH3 in dioxane (52 mL) is added. Stirring is continued at rt for 2 h before the mixture is again cooled to 0° C. Pyridine (4.35 g, 44.8 mmol) followed by trifluoroacetic anhydride (9.29 g, 44.2 mmol) is carefully added and the reaction mixture is stirred for 2 h while warming to rt. The mixture is then stirred at 70° C. for 15 h, cooled to rt, diluted with DCM and washed with 10% aq. citric acid solution followed by sat. aq. Na2CO3-solution. The org. extract is dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to give 2-(ethyl-methyl-amino)-6-methyl-isonicotinonitrile (257 mg) as a pale yellow oil; LC-MS: tR=0.58 min, [M+1]+=176.09.
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