6-(2-Biphenyl-4-yl-3-cyclopentyl-propionylamino)-nicotinic acid methyl ester → 2-biphenyl-4-yl-3-cyclopentyl-N-(5-hydroxymethyl-pyridin-2-yl)-propionamide

HRID 1935244Notes

Reaction equation

HRID 1935244 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:31])[CH:12]([C:19]2[CH:24]=[CH:23][C:22]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[CH:21][CH:20]=2)[CH2:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)=[N:6][CH:5]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C(OCC)C>[C:22]1([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH:21]=[CH:20][C:19]([CH:12]([CH2:13][CH:14]2[CH2:18][CH2:17][CH2:16][CH2:15]2)[C:11]([NH:10][C:7]2[CH:8]=[CH:9][C:4]([CH2:3][OH:2])=[CH:5][N:6]=2)=[O:31])=[CH:24][CH:23]=1

Participants

4

Reactant 2

HCID 101134046-(2-Biphenyl-4-yl-3-cyclopentyl-propionylamino)-nicotinic acid methyl esterHCID 21226445Aluminium lithium hydride

Product 1

HCID 101578322-biphenyl-4-yl-3-cyclopentyl-N-(5-hydroxymethyl-pyridin-2-yl)-propionamideYield 36%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 6-(2-biphenyl-4-yl-3-cyclopentyl-propionylamino)-nicotinic acid methyl ester (prepared in Example 22, 100 mg, 0.23 mmol) in diethyl ether (3 mL) at 0° C. under nitrogen was slowly treated with lithium aluminum hydride powder (12 mg, 0.30 mmol). The resulting reaction mixture continued to stir at 0° C. and was allowed to gradually warm to 25° C. The reaction mixture was then stirred at 25° C. over a period of 64 h. The reaction mixture was slowly quenched by the dropwise addition of water (5 mL). The resulting reaction mixture was partitioned between water and ethyl acetate, and the layers were separated. The aqueous layer was further extracted with ethyl acetate (1×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/2 hexanes/ethyl acetate) afforded 2-biphenyl-4-yl-3-cyclopentyl-N-(5-hydroxymethyl-pyridin-2-yl)-propionamide (33 mg, 36%) as a white solid: mp 67-70° C.; EI-HRMS m/e calcd for C26H28N2O2 (M+) 400.2151, found 400.2147.

Workup

  1. customThe resulting reaction mixture
  2. temperatureto gradually warm to 25° C
  3. stirringThe reaction mixture was then stirred at 25° C. over a period of 64 h
  4. customThe reaction mixture was slowly quenched by the dropwise addition of water (5 mL)
  5. customThe resulting reaction mixture
  6. customwas partitioned between water and ethyl acetate
  7. customthe layers were separated
  8. extractionThe aqueous layer was further extracted with ethyl acetate (1×25 mL)
  9. dry with materialThe combined organic extracts were dried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-cacb5173cf424d7f8774e4209a93d034
Source dataset
uspto-grants-2002_05
Patent number
US06384220B2

Reaction notes

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