Cesium carbonate → HCID 57504901, compound

HRID 2060771Notes

Reaction equation

HRID 2060771 reaction equation
Br[C:2]1[C:3]([F:27])=[CH:4][C:5]([F:26])=[C:6]([C:8]23[CH2:17][CH2:16][O:15][CH2:14][CH:13]2[CH2:12][S:11][C:10]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[N:9]3)[CH:7]=1.[N:28]1[CH:33]=[C:32](B(O)O)[CH:31]=[N:30][CH:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.C(O)C.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:26][C:5]1[CH:4]=[C:3]([F:27])[C:2]([C:32]2[CH:33]=[N:28][CH:29]=[N:30][CH:31]=2)=[CH:7][C:6]=1[C@:8]12[CH2:17][CH2:16][O:15][CH2:14][CH:13]1[CH2:12][S:11][C:10]([NH:18][C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[N:9]2

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 57504902HCID 57504902, compound

Product 1

HCID 57504901HCID 57504901, compoundYield 86.2%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
97 °C

Procedure

A mixture of tert-butyl 8a-(5-bromo-2,4-difluorophenyl)-4,4a,5,7,8,8a-hexahydropyrano[4,3-d][1,3]thiazin-2-ylcarbamate (0.300 g, 0.647 mmol) in 1,2-dimethoxyethane (10 mL), ethanol (4 mL) and water (5 mL) is purged with nitrogen and heated to 97° C. Pyrimidine-5-boronic acid (0.655 g, 5.18 mmol), cesium carbonate (1.90 g, 5.83 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.091 g, 0.129 mmol) is added in a single portion and the reaction is heated at 97° C. for 20 minutes. The reaction is cooled, diluted with water, and extracted with EtOAc. The organic layer is dried over Na2SO4 and the crude product is purified by silica gel chromatography eluting with a linear gradient of 5% to 100% EtOAc in hexanes to give the title compound (0.258 g, 86%). ES/MS (m/e): 463 (M+1).

Workup

  1. customis purged with nitrogen
  2. temperaturethe reaction is heated at 97° C. for 20 minutes
  3. temperatureThe reaction is cooled
  4. extractionextracted with EtOAc
  5. dry with materialThe organic layer is dried over Na2SO4
  6. customthe crude product is purified by silica gel chromatography
  7. washeluting with a linear gradient of 5% to 100% EtOAc in hexanes

Sources & evidence

ORD record
ord-4956e5b3fc384da7b7a1ef97194ed620
Source dataset
uspto-grants-2012_10
Patent number
US08278441B2

Reaction notes

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