2-AMINO-5-BROMOISONICOTINONITRILE synthesis

Yield: 78%

Reaction Conditions:

with N-Bromosuccinimide in N,N-dimethyl-formamide at -18; for 1 h;

Steps:

3.2.1
Step 2.1 : 2-Amino-5-bromo-isonicotinonitrile.A solution of 2-amino-isonicotinonitrile (10.0 g, 83.9 mmol) in DMF (20 mL) was cooled to -18°C (ice / MeOH bath), treated with NBS (16.5 g, 92.3 mmol), and stirred at -18°C for 1 h. The reaction mixture was diluted in AcOEt (500 mL) and washed with water {200 mL). The aqueous phase was separated and extracted with AcOEt (2 x 500 ml). The combined organic fractions were dried over Na_∑SO/_t, filtered and evaporated. The residue was purified by Combi-Flash Companion (Isco Inc.) column chromatography (SiO₂; gradient elution, [hexane / DCM 1 :1] / TBME 98:2 → 6:4) to yield the title compound (13.0 g, 65.6 mmol, 78%) as a pale yellow solid. MS: 199 [M+1]⁺ ; HPLC: _et = 1.13; TLC: R_F 0.39 (hexane / DCM / TBME 1 :1 :2).

References:

NOVARTIS AG;NOVARTIS PHARMA GMBH WO2007/113226, 2007, A1 Location in patent:Page/Page column 85-86