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

HRID 2296960Notes

Reaction equation

HRID 2296960 reaction equation
C[O:2][C:3](=[O:35])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:34])[CH:12]([C:19]2[CH:24]=[CH:23][C:22]([NH:25]C(C3C=NC=CC=3)=O)=[CH:21][CH:20]=2)[CH2:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[N:6][CH:5]=1.[OH-:36].[Li+].[OH2:38]>O1CCCC1>[CH:14]1([CH2:13][CH:12]([C:19]2[CH:24]=[CH:23][C:22]([N+:25]([O-:38])=[O:36])=[CH:21][CH:20]=2)[C:11]([NH:10][C:7]2[CH:8]=[CH:9][C:4]([C:3]([OH:2])=[O:35])=[CH:5][N:6]=2)=[O:34])[CH2:18][CH2:17][CH2:16][CH2:15]1

Participants

5

Reactant 3

HCID 962WaterHCID 3939Lithium HydroxideHCID 102055406-(3-Cyclopentyl-2-{4-[(pyridine-3-carbonyl)-amino]-phenyl}-propionylamino)-nicotinic acid methyl ester

Product 1

HCID 223150786-[3-Cyclopentyl-2-(4-nitro-phenyl)-propionylamino]-nicotinic acidYield 7.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-0885a0fd202342c1a6366d99e136b08b
Source dataset
uspto-grants-2002_12
Patent number
US06489485B2

Reaction notes

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