Potassium Carbonate → (2R)-4-{5-Fluoro-2-oxo-4-[4-(2H-tetrazol-2-yl)phenyl]pyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

HRID 1625020Notes

Reaction equation

HRID 1625020 reaction equation
C(=O)([O-])[O-].[K+].[K+].CC1(C)C(C)(C)OB([C:15]2[CH:20]=[CH:19][C:18]([N:21]3[N:25]=[N:24][CH:23]=[N:22]3)=[CH:17][CH:16]=2)O1.[F:27][C:28]1[C:29](I)=[CH:30][C:31](=[O:52])[N:32]([CH2:34][CH2:35][C@@:36]([CH3:51])([S:47]([CH3:50])(=[O:49])=[O:48])[C:37]([NH:39][O:40][CH:41]2[CH2:46][CH2:45][CH2:44][CH2:43][O:42]2)=[O:38])[CH:33]=1>O1CCOCC1.O.[Pd]>[F:27][C:28]1[C:29]([C:15]2[CH:16]=[CH:17][C:18]([N:21]3[N:25]=[N:24][CH:23]=[N:22]3)=[CH:19][CH:20]=2)=[CH:30][C:31](=[O:52])[N:32]([CH2:34][CH2:35][C@@:36]([CH3:51])([S:47]([CH3:50])(=[O:48])=[O:49])[C:37]([NH:39][O:40][CH:41]2[CH2:46][CH2:45][CH2:44][CH2:43][O:42]2)=[O:38])[CH:33]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 706645862-[4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2H-tetrazoleHCID 86670637(2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide

Product 1

HCID 86670636(2R)-4-{5-Fluoro-2-oxo-4-[4-(2H-tetrazol-2-yl)phenyl]pyridin-1(2H)-yl}-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamideYield 98.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
80 °C

Procedure

Pd EnCat™ (317 mg, 0.10 mmol) was added to a mixture of potassium carbonate (393 mg, 2.84 mmol), 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-2H-tetrazole (258.4 mg, 0.95 mmol), and (2R)-4-(5-fluoro-4-iodo-2-oxopyridin-1(2H)-yl)-2-methyl-2-(methylsulfonyl)-N-(tetrahydro-2H-pyran-2-yloxy)butanamide (490 mg, 0.95 mmol), T3, in 1,4-dioxane:water (4:1, 10 mL). The reaction was heated to 80° C. and stirred at this temperature overnight. The reaction was filtered through celite, and the filter pad was washed with methanol (250 mL). The combined filtrates were concentrated under reduced pressure, and the resulting crude material was purified via flash chromatography using an eluent of EtOAc in n-heptane (20-100%) and methanol in EtOAc (0-10%) to afford the title compound as a light tan solid (500 mg, 98%). MS (LCMS) m/z 534.4 (M−1). 0

Workup

  1. filtrationThe reaction was filtered through celite
  2. washthe filter pad was washed with methanol (250 mL)
  3. concentrationThe combined filtrates were concentrated under reduced pressure
  4. customthe resulting crude material was purified via flash chromatography

Sources & evidence

ORD record
ord-eae5b89eb4744da8b995c4f625da7099
Source dataset
uspto-grants-2014_07
Patent number
US08779148B2

Reaction notes

Loading…