1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 6,6-dimethyl-4-{3-methyl-2-[(2-methyl-pyridine-3-carbonyl)-amino]-butyl}-morpholine-3-carboxylic acid (6-chloro-9H-beta-carbolin-8-yl)-amide

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Reaction Steps

To a solution of 4-(2-amino-3-methyl-butyl)-6,6-dimethyl-morpholine-3-carboxylic acid (6-chloro-9H-β-carbolin-8-yl)-amide (1.47 g, 3.31 mmol) in pyridine (35 mL) was added 2-methyl-nicotinic acid (544 mg, 3.97 mmol) and EDCI (1.02 g, 5.30 mmol). The solution was stirred 6.5 hours at room temperature, then diluted with water (100 mL). The mixture was poured into a separatory funnel and diluted further with water (50 mL) and EtOAc (150 mL). The layers were shaken and separated. The aqueous layer was extracted with EtOAc (3×50 mL), then the combined organic layers were washed with brine. The organic layer was dried over magnesium sulfate, filtered, and concentrated to yield an orange semi-solid residue which was purified via column chromatography. The resulting yellow solid was placed on the high-vacuum pump overnight, after which 1.43 g of 6,6-dimethyl-4-{3-methyl-2-[(2-methyl-pyridine-3-carbonyl)-amino]-butyl}-morpholine-3-carboxylic acid (6-chloro-9H-β-carbolin-8-yl)-amide was obtained (77% yield). 1H-NMR (DMSO-d6, 300 MHz) δ 11.32 (s, 1); 10.08 (s, 1); 9.02 (s, 1); 8.46 (dd, 1); 8.38 (d, 1); 8.21-8.14 (m, 3); 7.97 (d, 1); 7.64 (dd, 1); 7.23 (dd, 1); 4.23-4.14 (m, 1); 3.99-3.87 (m, 2); 3.22-3.19 (m, 1): 3.02 (d, 1); 2.85 (dd, 1); 2.52 (s, 3); 2.30 (dd, 1); 2.11 (d, 1); 2.05-1.95 (m, 1); 1.32 (s, 3); 1.21 (s, 3); 0.93 (d, 3); 0.86 (d, 3). NH4OAc standard conditions. DAD Rf=1.67 min. M+H=563.

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