Ethanol → HCID 57948930, compound

HRID 1992290Notes

Reaction equation

HRID 1992290 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@:8]2([CH3:23])[CH2:13][C@@H:12]([CH3:14])[S:11][C:10]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.C(O)C.[N:27]1[CH:32]=[C:31](B(O)O)[CH:30]=[N:29][CH:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.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>[C:18]([O:17][C:16](=[O:22])[NH:15][C:10]1[S:11][C@H:12]([CH3:14])[CH2:13][C@@:8]([CH3:23])([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([C:31]3[CH:32]=[N:27][CH:28]=[N:29][CH:30]=3)[CH:3]=2)[N:9]=1)([CH3:21])([CH3:20])[CH3:19]

Participants

8

Reactant 4

HCID 702EthanolHCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 57948963HCID 57948963, compound

Product 1

HCID 57948930HCID 57948930, compoundYield 39%

Reagents, catalysts & solvents 3

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

Procedure

To a 100° C. solution of tert-butyl (4S,6R)-4-(3-bromophenyl)-4,6-dimethyl-5,6-dihydro-4H-1,3-thiazin-2-ylcarbamate in 1,2-dimethoxyethane: water: ethanol [(3:1.5:1), 12 mL] is added, in a single portion, pyrimidine-5-boronic acid (128 mg, 5.9 mmoles, 2.5 equiv), bis(triphenylphosphine)palladium(II) chloride (29 mg, 41 μmoles, 0.1 equiv) and cesium carbonate (1.24 g, 1.24 mmoles, 3 equiv). After 20 minutes, the reaction is cooled to ambient temperature, diluted with water, and extracted with dichloromethane. The organic phase is dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel flash column chromatography eluting with a linear gradient of hexane to hexane:ethyl acetate (5:2) over 20 minutes to give the title compound (39% yield): MS (m/z): 399 (M+1).

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialThe organic phase is dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified by silica gel flash column chromatography
  6. washeluting with a linear gradient of hexane to hexane:ethyl acetate (5:2) over 20 minutes

Sources & evidence

ORD record
ord-ca5cdfdf9af84fa4839d26dcaf274f08
Source dataset
uspto-grants-2010_01
Patent number
US07648983B2

Reaction notes

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