Nitrogen → 1-{5-Chloro-3-[2-(dimethylamino)pyrimidin-5-yl]-2-methoxy-4-methylphenyl}ethanone

HRID 510868Notes

Reaction equation

HRID 510868 reaction equation
Br[C:2]1[C:3]([O:13][CH3:14])=[C:4]([C:10](=[O:12])[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].[CH3:15][N:16]([CH3:32])[C:17]1[N:22]=[CH:21][C:20](B2OC(C)(C)C(C)(C)O2)=[CH:19][N:18]=1.O.N#N>O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:9][C:6]1[C:7]([CH3:8])=[C:2]([C:20]2[CH:19]=[N:18][C:17]([N:16]([CH3:32])[CH3:15])=[N:22][CH:21]=2)[C:3]([O:13][CH3:14])=[C:4]([C:10](=[O:12])[CH3:11])[CH:5]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 962WaterHCID 16414215N,N-Dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amineHCID 866667591-(3-Bromo-5-chloro-2-methoxy-4-methylphenyl)ethanone

Product 1

HCID 866667951-{5-Chloro-3-[2-(dimethylamino)pyrimidin-5-yl]-2-methoxy-4-methylphenyl}ethanoneYield 52.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A biphasic solution of 1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethanone (0.10 g, 0.36 mmol) and N,N-dimethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (0.11 g, 0.43 mmol) in 1,4-dioxane (1.2 mL) and 10% sodium carbonate in water (0.57 mL, 0.54 mmol) was bubbled with N2 to degas. After tetrakis(triphenylphosphine)palladium(0) (17 mg, 0.014 mmol) was added, the mixture was bubbled with N2 for 5 min. and heated at 100° C. overnight. The mixture was cooled to r.t. and diluted with ethyl acetate. The layers were separated and the aq. layer was extracted with more ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel column, eluting with 0-30% of ethyl acetate in hexane, to give the desired product (60 mg, 50%). LCMS calculated for C16H19ClN3O2 (M+H)+: m/z=320.1. found: 320.1.

Workup

  1. customto degas
  2. customthe mixture was bubbled with N2 for 5 min.
  3. temperatureThe mixture was cooled to r.t.
  4. additiondiluted with ethyl acetate
  5. customThe layers were separated
  6. extractionthe aq. layer was extracted with more ethyl acetate
  7. washThe combined extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified on silica gel column
  12. washeluting with 0-30% of ethyl acetate in hexane

Sources & evidence

ORD record
ord-0d46aaf38edf45d7a9175210247e5293
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

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