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 468625ノート

反応式

HRID 468625 の反応式
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

参加物

6

反応物 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

生成物 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)butanamide収率 98.5%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 218864351,4-Dioxane--water (1/1)溶媒

反応条件

温度
80 °C

実験手順

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

後処理

  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

出典と根拠

ORDレコード
ord-568160da01a24dcc97f91f00b540c621
出典データセット
uspto-grants-2014_01
特許番号
US08624034B2

反応ノート

読み込み中…