Potassium Carbonate → HCID 90009212, compound

HRID 531261Notes

Reaction equation

HRID 531261 reaction equation
Br[C:2]1[C:3]([CH2:10][N:11]2[C@@H:15]([CH3:16])[C@@H:14]([C:17]3[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([F:27])[CH:18]=3)[O:13][C:12]2=[O:28])=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=1.[C:29]([O:33][C:34]([C:36]1[CH:41]=[CH:40][C:39]([C:42]2[CH:43]=[C:44](B(O)O)[C:45]([O:48][CH3:49])=[N:46][CH:47]=2)=[C:38]([CH3:53])[CH:37]=1)=[O:35])([CH3:32])([CH3:31])[CH3:30].C(=O)([O-])[O-].[K+].[K+]>C1COCC1.[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:27][C:19]1[CH:18]=[C:17]([C@H:14]2[O:13][C:12](=[O:28])[N:11]([CH2:10][C:3]3[C:2]([C:44]4[CH:43]=[C:42]([C:39]5[CH:40]=[CH:41][C:36]([C:34]([O:33][C:29]([CH3:31])([CH3:32])[CH3:30])=[O:35])=[CH:37][C:38]=5[CH3:53])[CH:47]=[N:46][C:45]=4[O:48][CH3:49])=[CH:7][N:6]=[C:5]([S:8][CH3:9])[N:4]=3)[C@H:15]2[CH3:16])[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 90009169HCID 90009169, compound2×HCID 123228619{5-[4-(tert-Butoxycarbonyl)-2-methylphenyl]-2-methoxypyridin-3-yl}boronic acid2×

Product 1

HCID 90009212HCID 90009212, compoundYield 88.1%

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (4S,5R)-3-{[5-bromo-2-(methylsulfanyl)pyrimidin-4-yl]methyl}-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 10, 150 mg, 0.312 mmol) in THF (3.0 mL) was added {5-[4-(tert-butoxycarbonyl)-2-methylphenyl]-2-methoxypyridin-3-yl}boronic acid (INTERMEDIATE 32, 129 mg, 0.375 mmol), 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (10.2 mg, 0.016 mmol), and aqueous potassium carbonate (0.468 mL, 2.0 M). The mixture was degassed, flushed with nitrogen and heated to 90° C. for 45 minutes, then allowed to stir at room temperature overnight. The reaction was diluted with ethyl acetate, washed with water, brine, dried over sodium sulfate, filtered and the filtrate concentrated. The crude product was purified by column chromatography to afford tert-butyl 4-{5-[4-({(4S,5R)-5-[3-fluoro-5-(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-2-(methylsulfanyl)pyrimidin-5-yl]-6-methoxypyridin-3-yl}-3-methylbenzoate (192 mg, 0.275 mmol). LCMS (M+H)+: 699.1

Workup

  1. customThe mixture was degassed
  2. customflushed with nitrogen
  3. additionThe reaction was diluted with ethyl acetate
  4. washwashed with water, brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe filtrate concentrated
  8. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-daeabe7aa36e41dea1fa71344f951ffa
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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