Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 2-(7-Cyano-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)-3-fluorophenyl]ethyl}acetamide

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Reaction Steps

2-(7-Cyano-1H-benzimidazol-1-yl)-N-{1-[4-(1-cyano-1-methylethyl)-3-fluorophenyl]ethyl}acetamide is synthesized according to example 1 by mixing 2-[4-(1-Aminoethyl)-2-fluorophenyl]-2-methylpropanenitrile hydrochloride (260 mg, 0.94 mmol) prepared according to scheme 7, (7-cyano-1H-benzimidazol-1-yl)acetic acid (200 mg, 0.94 mmol) prepared according to scheme 3 and DMAP (228 mg, 1.89 mmol, 1.00 mL) and HATU (358 mg, 2.49 mmol) in DMF (5.0 mL). The product is purified by HPLC: Waters prep LCMS, Flow rate: 27 ml/min, Column: SynerSi (4μ) Polar RP, 21.2×50 mm, Mobile phase: A=water (0.05% TFA) B=MeCN, Gradient used 40% to 60% B in A, in 10 min. The fractions are combined, NaOH 1N is added and the desired compound is extracted with ethyl acetate. The combined organic fractions are concentrated under reduced pressure to yield the product (69 mg, 1.77 mmol, 19%). 1H NMR (400 MHz, METHANOL-D4) δ ppm 1.50 (d, J=7.03 Hz, 3H) 1.72-1.78 (m, 6H) 5.02 (q, J=6.97 Hz, 1H) 5.31 (d, J=17.58 Hz, 1H) 5.36 (d, J=17.58 Hz, 1H) 7.17-7.25 (m, 2H) 7.39 (dd, J=8.20, 7.62 Hz, 1H) 7.43 (t, J=8.40 Hz, 1H) 7.67 (dd, J=7.62, 0.78 Hz, 1H) 7.97 (dd, J=8.20, 0.98 Hz, 1H) 8.26 (s, 1H); MS [M+H], calcd: 390.2. found: 390.3.

Provenance & Evidence