Water → 6-[3-Cyclopentyl-2-(4-nitro-phenyl)-propionylamino]-nicotinic acid

Temperature

25 °C

A solution of 6-(3-cyclopentyl-2-{4-[(pyridine-3-carbonyl)-amino]-phenyl}-propionylamino)-nicotinic acid methyl ester (prepared in Example 16, 87.2 mg, 0.18 mmol) in tetrahydrofuran (8 mL) and water (2 mL) was treated with lithium hydroxide (17.0 mg, 0.41 mmol). The reaction was stirred at 25° C. for 20 h. At this time, the reaction was concentrated in vacuo. The residue was diluted with water (25 mL) and extracted with diethyl ether (1×20 mL). The aqueous layer was acidified to pH=1 with a 3N aqueous hydrochloric acid solution and was extracted with methylene chloride (3×50 mL). The combined organic extracts were washed with water (1×50 mL) and a saturated aqueous sodium chloride solution (2×50 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. High pressure liquid chromatography (Chromegasphere SI-60, 10 μM, 60 Å, 25 cm×23 cm ID, 100% ethyl acetate with acetic acid) afforded 6-[3-cyclopentyl-2-(4-nitro-phenyl)-propionylamino]-nicotinic acid (6.4 mg, 7.5%) as a pale yellow oil: EI-HRMS m/e calcd for C16H26N4O4 (M+) 458.1954, found 458.1967.

1. concentrationAt this time, the reaction was concentrated in vacuo
2. additionThe residue was diluted with water (25 mL)
3. extractionextracted with diethyl ether (1×20 mL)
4. extractionwas extracted with methylene chloride (3×50 mL)
5. washThe combined organic extracts were washed with water (1×50 mL)
6. dry with materiala saturated aqueous sodium chloride solution (2×50 mL), dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo

ORD record

ord-0885a0fd202342c1a6366d99e136b08b

Source dataset

uspto-grants-2002_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06489485B2