Sodium Bicarbonate → 4'-Hydroxy-6-trifluoromethyl-3',4',5',6'-tetrahydro-2'h-[2,4']bipyridinyl-1'-carboxylic acid(7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide

HRID 550820Notes

Reaction equation

HRID 550820 reaction equation
[F:1][C:2]([F:17])([F:16])[C:3]1[N:8]=[C:7]([C:9]2([OH:15])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:6]=[CH:5][CH:4]=1.C1([O:24][C:25](=O)[NH:26][C:27]2[S:28][C:29]3[N:30]=[CH:31][N:32]=[C:33]([O:36][CH3:37])[C:34]=3[N:35]=2)C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(#N)C>[CH3:37][O:36][C:33]1[C:34]2[N:35]=[C:27]([NH:26][C:25]([N:12]3[CH2:11][CH2:10][C:9]([OH:15])([C:7]4[CH:6]=[CH:5][CH:4]=[C:3]([C:2]([F:1])([F:16])[F:17])[N:8]=4)[CH2:14][CH2:13]3)=[O:24])[S:28][C:29]=2[N:30]=[CH:31][N:32]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 59011944(7-Methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-carbamic acid phenyl esterHCID 590119804-(6-(Trifluoromethyl)pyridin-2-yl)piperidin-4-ol

Product 1

HCID 248299584'-Hydroxy-6-trifluoromethyl-3',4',5',6'-tetrahydro-2'h-[2,4']bipyridinyl-1'-carboxylic acid(7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amideYield 17.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 6-trifluoromethyl-2′,3′,5′,6′-tetrahydro-1′H-[2,4′]bipyridinyl-4′-ol (320 mg, 1.30 mmol) in acetonitrile (15 mL) was treated with (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-carbamic acid phenyl ester (360 mg, 1.18 mmol). The mixture was stirred at reflux for 2 h. At this time, the reaction was poured into a saturated aqueous sodium bicarbonate solution. The aqueous layer was extracted with methylene chloride. The organics were washed with a saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 98/2 methylene chloride/methanol) afforded 4′-hydroxy-6-trifluoromethyl-3′,4′,5′,6′-tetrahydro-2′H-[2,4′]bipyridinyl-1′-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (94 mg, 17%) as a white solid; LRMS for C18H17F3N6O3S (M+H)+ at m/z=454. The NMR spectrum obtained on the sample is compatible with its structure.

Workup

  1. temperatureat reflux for 2 h
  2. extractionThe aqueous layer was extracted with methylene chloride
  3. washThe organics were washed with a saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-962cdeab127e4fb99fd355165ebf5f32
Source dataset
uspto-grants-2011_05
Patent number
US07947692B2

Reaction notes

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