Cesium carbonate → HCID 57948947, compound

HRID 1992295Notes

Reaction equation

HRID 1992295 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@:8]2([CH3:24])[CH2:13][C@@H:12]([CH2:14][OH:15])[S:11][C:10]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[N:25]1[CH:30]=[C:29](B(O)O)[CH:28]=[N:27][CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.C(O)C.CCOC(C)=O.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>[OH:15][CH2:14][C@H:12]1[S:11][C:10]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[N:9][C@:8]([CH3:24])([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([C:29]3[CH:30]=[N:25][CH:26]=[N:27][CH:28]=3)[CH:3]=2)[CH2:13]1

Participants

9

Reactant 3

HCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 57948949HCID 57948949, compound

Product 1

HCID 57948947HCID 57948947, compoundYield 29%

Reagents, catalysts & solvents 5

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a 110° C. solution of (+/−) tert-butyl (4S,6S)-4-(3-bromophenyl)-6-(hydroxymethyl)-4-methyl-5,6-dihydro-4H-1,3-thiazin-2-ylcarbamate (150 mg, 0.36 mmol) in 1,2-dimethoxyethane (4.5 mL), ethanol (1.5 mL), and water (2.3 mL) is added pyrimidine-5-boronic acid (112 mg, 0.90 mmoles, 2.5 equiv), cesium carbonate (353 mg, 1.08 mmol, 3 equiv), and bis(triphenylphosphine)palladium(II) chloride (25 mg, 0.036 mmol, 0.1 equiv). The reaction is stirred at 110° C. After 20 minutes, the reaction mixture is diluted with EtOAc and H2O. The layers are separated and the aqueous phase is extracted with EtOAc. The combined organic layers are dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue is purified by column chromatography on silica gel (5% MeOH/DCM) to give the title compound (29% yield): MS (m/z): 415 (M+1)

Workup

  1. customThe layers are separated
  2. extractionthe aqueous phase is extracted with EtOAc
  3. dry with materialThe combined organic layers are dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue is purified by column chromatography on silica gel (5% MeOH/DCM)

Sources & evidence

ORD record
ord-8e574e12f46748e0aac7a6027183d497
Source dataset
uspto-grants-2010_01
Patent number
US07648983B2

Reaction notes

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