Citric Acid → HCID 86610682, compound

HRID 506400Notes

Reaction equation

HRID 506400 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[N:13][C:14]([O:18][CH3:19])=[CH:15][CH:16]=2)[C@@H:11]([NH:20][C:21]2[N:26]=[C:25]([CH2:27][C:28]3[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=3)[C:24]([N:42]3[CH2:47][CH2:46][CH:45]([C:48]([O:50]CC)=[O:49])[CH2:44][CH2:43]3)=[CH:23][N:22]=2)[CH2:10][C@H:9]1[CH2:53][CH3:54])=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[N:13][C:14]([O:18][CH3:19])=[CH:15][CH:16]=2)[C@@H:11]([NH:20][C:21]2[N:26]=[C:25]([CH2:27][C:28]3[CH:33]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:31]=[C:30]([C:38]([F:40])([F:41])[F:39])[CH:29]=3)[C:24]([N:42]3[CH2:43][CH2:44][CH:45]([C:48]([OH:50])=[O:49])[CH2:46][CH2:47]3)=[CH:23][N:22]=2)[CH2:10][C@H:9]1[CH2:53][CH3:54])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 311Citric AcidHCID 14798Sodium HydroxideHCID 86610680HCID 86610680, compound

Product 1

HCID 86610682HCID 86610682, compoundYield 66.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

(2R,4S)-4-{[3,5-Bis(trifluoromethyl)benzyl]-[5-(4-ethoxycarbonyl-piperidin-1-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid tert-butyl ester (120 mg) is dissolved in 1,4-dioxane (1 ml), and thereto is added 1M aqueous NaOH solution (1 ml). The mixture is stirred at 50° C. for 1 hour. After 10% aqueous citric acid solution is added to the reaction mixture, the mixture is extracted with ethyl acetate. The organic layer is washed with saturated brine and dried over magnesium sulfate, then concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; chloroform:methanol=19:1) to give (2R,4S)-4-{[3,5-bis(trifluoromethyl)-benzyl]-[5-(4-carboxypiperidin-1-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid tert-butyl ester (77 mg). MS (m/z): 739 [M+H]+.

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. washThe organic layer is washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by column chromatography (silica gel; chloroform:methanol=19:1)

Sources & evidence

ORD record
ord-e2f44687778445eda38da314a1d9c29a
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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