Cesium carbonate → HCID 57948966, compound

HRID 1992276Notes

Reaction equation

HRID 1992276 reaction equation
Br[C:2]1[C:3]([F:17])=[CH:4][C:5]([F:16])=[C:6]([C@:8]2([CH3:15])[CH2:13][CH2:12][S:11][C:10]([NH2:14])=[N:9]2)[CH:7]=1.[N:18]1[CH:23]=[C:22](B(O)O)[CH:21]=[N:20][CH:19]=1.[C:27](=[O:30])([O-])[O-:28].[Cs+].[Cs+]>COCCOC.O.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>[C:6]([O:28][C:27](=[O:30])[NH:14][C:10]1[S:11][CH2:12][CH2:13][C@:8]([C:6]2[CH:7]=[C:2]([C:22]3[CH:23]=[N:18][CH:19]=[N:20][CH:21]=3)[C:3]([F:17])=[CH:4][C:5]=2[F:16])([CH3:15])[N:9]=1)([CH3:8])([CH3:7])[CH3:5]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 57948952HCID 57948952, compound

Product 1

HCID 57948966HCID 57948966, compoundYield 67%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 86587095Dimethoxyethane ethanol waterSolvent

Procedure

To a 100° C. solution of (S)-4-(5-bromo-2,4-difluorophenyl)-4-methyl-5,6-dihydro-4H-1,3-thiazin-2-amine (12.6 g, 29.9 mmol, 1 equiv) in 1,2-dimethoxyethane:water:ethanol (15:7:5, 300 mL) is added a pyrimidine-5-boronic acid (25 g, 203 mmoles, 6.8 equiv) followed by cesium carbonate (58 g, 180 mmoles, 6 equiv) and bis(triphenylphosphine)palladium(II) chloride (4.2 g, 6.0 moles, 0.2 equiv). After 40 minutes, the reaction is cooled to ambient temperature, diluted with water, and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel chromatography eluting with a step gradient of hexanes:ethyl acetate (7:3) to hexanes:ethyl acetate (1:1) to give the title compound (67% yield): MS (m/z): 421 (M+1).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialThe organic phase is dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified by silica gel chromatography
  6. washeluting with a step gradient of hexanes:ethyl acetate (7:3) to hexanes:ethyl acetate (1:1)

Sources & evidence

ORD record
ord-7627431c72394268b43f204e879b2454
Source dataset
uspto-grants-2010_01
Patent number
US07648983B2

Reaction notes

Loading…