Triethylamine → (+/-)-3-{4-[(3,3-Di methyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid ethyl ester

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Reaction Steps

(+/−)-4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoic acid (Intermediate 26) (37 mg, 0.099 mmol) was combined with 1-hydrobenzotriazole hydrate (23.0 mg, 0.149 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (29.0 mg, 0.149 mmol), and beta-alanine ethyl ester hydrochloride (18.0 mg, 0.119 mmol). Anhydrous dichloromethane (5 mL) was added followed by triethylamine (0.027 mL, 0.198 mmol). The solution was stirred at room temperature for 3 d before partitioning between ethyl acetate and aq. sat. ammonium chloride. The separated aqueous layer was extracted with ethyl acetate and the combined organics dried over MgSO4. Purification by silica gel flash chromatography (ethyl acetate/heptane) gave (+/−)-3-{4-[(3,3-dimethyl-cyclobutyl)-(3-methyl-quinolin-2-ylamino)-methyl]-benzoylamino}-propionic acid ethyl ester (37.9 mg) as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J=8.2 Hz, 2 H) 7.59 (t, J=3.9 Hz, 2 H) 7.46-7.52 (m, 3 H) 7.37-7.45 (m, 1 H) 7.11-7.19 (m, 1 H) 6.75 (t, J=5.8 Hz, 1 H) 5.32 (dd, J=9.7, 6.7 Hz, 1 H) 4.75 (d, J=6.6 Hz, 1 H) 4.10-4.21 (m, 2 H) 3.70 (q, J=6.0 Hz, 2 H) 2.55-2.74 (m, 3 H) 2.29 (s, 3 H) 1.96 (ddd, J=11.1, 8.2, 2.9 Hz, 1 H) 1.75-1.84 (m, 1 H) 1.64-1.73 (m, 2 H) 1.26 (m, 3 H) 1.16 (s, 3 H) 1.09 (s, 3 H); MS (M+1): 474.7.

Provenance & Evidence