Water → tert-Butyl 4-{5-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(3,3-difluoroazetidin-1-yl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3-methylbenzoate

HRID 531298Notes

Reaction equation

HRID 531298 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25](Br)=[CH:24][N:23]=[C:22]([N:27]4[CH2:30][C:29]([F:32])([F:31])[CH2:28]4)[N:21]=3)[C@H:14]2[CH3:33])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:36][O:37][C:38]1[N:43]=[CH:42][C:41]([C:44]2[CH:56]=[CH:55][C:47]([C:48]([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49])=[CH:46][C:45]=2[CH3:57])=[CH:40][C:39]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+].O>O1CCOCC1.[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([C:39]4[CH:40]=[C:41]([C:44]5[CH:56]=[CH:55][C:47]([C:48]([O:50][C:51]([CH3:53])([CH3:54])[CH3:52])=[O:49])=[CH:46][C:45]=5[CH3:57])[CH:42]=[N:43][C:38]=4[O:37][CH3:36])=[CH:24][N:23]=[C:22]([N:27]4[CH2:30][C:29]([F:32])([F:31])[CH2:28]4)[N:21]=3)[C@H:14]2[CH3:33])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 86704624(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5-bromo-2-(3,3-difluoroazetidin-1-yl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one2×HCID 89522254Tert-butyl 4-[6-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]-3-methylbenzoate2×

Product 1

HCID 124089233tert-Butyl 4-{5-[4-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(3,3-difluoroazetidin-1-yl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3-methylbenzoate

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
45 °C

Procedure

A solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[5-bromo-2-(3,3-difluoroazetidin-1-yl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 13, 200 mg, 0.348 mmol), tert-butyl 4-[6-methoxy-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]-3-methylbenzoate (INTERMEDIATE 31, 173 mg, 0.452 mmol) and potassium carbonate (144 mg, 1.04 mmol), in 1,4-dioxane (2 mL) and water (2.000 mL) was degassed, and refilled with nitrogen. Then, 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (11.3 mg, 0.017 mmol) was added, and the reaction was stirred at 45° C. for 2 hours. It was directly applied to preparative reverse phase HPLC, eluting with 10% to 100% acetonitrile in water, to give the title compound for step A as a white solid after lyophilization. LCMS (M+H)+: 794.05.

Workup

  1. additionrefilled with nitrogen
  2. washeluting with 10% to 100% acetonitrile in water

Sources & evidence

ORD record
ord-f15330b679324d7f8223c7c2a7bae5d0
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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