Ammonia → HCID 67104068, compound

HRID 273240Notes

Reaction equation

HRID 273240 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([CH2:12][CH2:13][OH:14])[CH:6]=[CH:5]2.[CH3:15][O:16][C:17]1[N:22]=[C:21]([O:23][CH3:24])[C:20](B(O)O)=[CH:19][N:18]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O.N>C(O)(C)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>[CH3:15][O:16][C:17]1[N:22]=[C:21]([O:23][CH3:24])[C:20]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[CH:8]=[C:7]([CH2:12][CH2:13][OH:14])[CH:6]=[CH:5]3)=[CH:19][N:18]=1

Participants

8

Reactant 4

HCID 222AmmoniaHCID 2736209(2,4-Dimethoxypyrimidin-5-yl)boronic acidHCID 22031701Potassium phosphate, tribasic, monohydrateHCID 251961662-(6-Bromonaphthalen-2-yl)ethan-1-ol

Product 1

HCID 67104068HCID 67104068, compoundYield 30%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of the product from Example 1E (0.1020 g, 0.41 mmol), 2,4-dimethoxypyrimidin-5-yl-boronic acid (0.0920 g, 0.50 mmol), dichlorobis (triphenylphosphine)-palladium (II) (0.0096 g, 0.014 mmol), and K3PO4.H2O in isopropyl alcohol (5 mL) and H2O (2 mL) was stirred at 65° C. for 2 hours. The reaction mixture was cooled to room temperature then concentrated under reduced pressure. The residue was partitioned between brine and ethyl acetate. The aqueous layer was washed with ethyl acetate, and the combined organic extracts were dried (MgSO4), and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (7:3 hexane/ethyl acetate). Fractions containing product were combined to provide (0.0376 g, 30% yield). 1H NMR (CDCl3, 300 MHz), δ 8.37 (s, 1H), 7.95 (s, 1H), 7.86-7.82 (d, J=6 Hz, 2H), 7.71 (s, 1H), 7.64-7.59 (d, J=9 Hz, 1H), 7.46-7.6 (s, J=9 Hz, 1H), 4.08 (s, 3H), 4.06 (s, 3H), 3.89-3.84 (t, J=7.5 Hz, 2H), 3.30-2.98 (t, J=7.5 Hz, 2H). MS (DCl—NH3) [M+H]+ at 311.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationthen concentrated under reduced pressure
  3. customThe residue was partitioned between brine and ethyl acetate
  4. washThe aqueous layer was washed with ethyl acetate
  5. dry with materialthe combined organic extracts were dried (MgSO4)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was purified by column chromatography (7:3 hexane/ethyl acetate)
  9. additionFractions containing product
  10. customto provide (0.0376 g, 30% yield)

Sources & evidence

ORD record
ord-86278b2b9ece4ef4a66e3a944aff3ed4
Source dataset
uspto-grants-2008_11
Patent number
US07456196B2

Reaction notes

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