Dichloromethane → HCID 57948937, compound

HRID 1992286Notes

Reaction equation

HRID 1992286 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@:9]2([CH3:26])[CH2:14][C:13]([CH3:16])([CH3:15])[S:12][C:11]([NH:17][C:18](=[O:25])[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[N:27]1[CH:32]=[C:31](B(O)O)[CH:30]=[N:29][CH:28]=1.C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>COCCOC.C(O)C.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[F:8][C:7]1[CH:6]=[CH:5][C:4]([C@:9]2([CH3:26])[CH2:14][C:13]([CH3:16])([CH3:15])[S:12][C:11]([NH:17][C:18](=[O:25])[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[N:10]2)=[CH:3][C:2]=1[C:31]1[CH:32]=[N:27][CH:28]=[N:29][CH:30]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 57948925HCID 57948925, compound

Product 1

HCID 57948937HCID 57948937, compoundYield 46%

Reagents, catalysts & solvents 4

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
97 °C

Procedure

To a 97° C. solution of (S)-N-(4-(3-bromo-4-fluorophenyl)-4,6,6-trimethyl-5,6-dihydro-4H-1,3-thiazin-2-yl)benzamide (0.067 g, 0.15 mmoles, 1.0 equiv) in 1,2-dimethoxyethane (1.5 mL), ethanol (0.7 mL) and water (1.0 mL) is added pyrimidine-5-boronic acid (0.095 g, 0.77 mmoles, 5.0 equiv), cesium carbonate (0.301 g, 0.92 mmoles, 6.1 equiv) and bis(triphenylphoshine)palladium (II) chloride (0.022 g, 0.03 mmoles, 0.2 equiv). The reaction mixture is stirred at 97° C. for 20 minutes. After cooling to room temperature, the reaction mixture is poured into water and extracted with ethyl acetate. The organic phase is dried over sodium sulfate, filtered, and concentrated under reduced pressure. The solvent is removed under reduced pressure and the residue is purified by silica gel flash column chromatography eluting with a linear gradient of dichloromethane to 15% ethyl acetate: dichloromethane to give the title compound (46% yield): MS (m/z): 435 (M+1).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic phase is dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe solvent is removed under reduced pressure
  7. customthe residue is purified by silica gel flash column chromatography
  8. washeluting with a linear gradient of dichloromethane to 15% ethyl acetate

Sources & evidence

ORD record
ord-332fad58e8364d4595c2f430ac0e285f
Source dataset
uspto-grants-2010_01
Patent number
US07648983B2

Reaction notes

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