Sodium Carbonate → HCID 178521624, compound

HRID 2047558Notes

Reaction equation

HRID 2047558 reaction equation
Br[C:2]1[CH:15]=[CH:14][C:5]2[N:6]=[C:7]([C@@H:9]3[CH2:12][C@H:11]([OH:13])[CH2:10]3)[S:8][C:4]=2[CH:3]=1.[N:16]1[CH:21]=[C:20](B(O)O)[CH:19]=[N:18][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+]>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.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C(O)C.O1CCOCC1>[N:16]1[CH:21]=[C:20]([C:2]2[CH:15]=[CH:14][C:5]3[N:6]=[C:7]([C@@H:9]4[CH2:12][C@H:11]([OH:13])[CH2:10]4)[S:8][C:4]=3[CH:3]=2)[CH:19]=[N:18][CH:17]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 178521623HCID 178521623, compound

Product 1

HCID 178521624HCID 178521624, compoundYield 84.6%

Reagents, catalysts & solvents 3

HCID 27342162-(Dicyclohexylphosphino)biphenylCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 22560076Dioxan ethanolSolvent

Conditions

Temperature
140 °C

Procedure

The product of Example 1D (100 mg, 0.35 mmole), pyrimidine-5-boronic acid (65 mg, 0.53 mmole), dichlorobis(triphenylphosphine)palladium(II) (14.8 mg, 0.0021 mmole), 2-(dicyclohexyl-phosphino)biphenyl (7.4 mg, 0.021 mmole), sodium carbonate (1 M solution, 0.53 ml, 0.53 mmole) and 2 ml of ethanol/dioxane (1:1) were mixed under N2 in a capped, sealed vial. The vial was sealed heated in the microwave for 10 minutes at 140° C. using a commercial microwave heating apparatus (i.e. the Emrys Creator). The reaction mixture was quenched with water and extracted with dichloromethane (4×5 ml). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product which was purified by column chromatography (10% methanol in dichloromethane) to give 80.4 mg (84.6% yield) of title compound. 1H NMR (300 MHz, CDCl3) δ ppm 9.25 (s, 1H), 9.03 (s, 2H), 8.14 (d, J=8.48 Hz, 1H), 8.07 (d, J=1.70 Hz, 1H), 7.67 (dd, J=8.48, 2.03 Hz, 1H), 4.40 (m, 1H), 3.50 (m, 1H), 3.01 (m, 2H), 2.46 (m, 2H), 2.17 (br s, 1H). MS: (M+H)+=284.

Workup

  1. customsealed vial
  2. customThe vial was sealed
  3. temperatureheating apparatus (i.e. the Emrys Creator)
  4. customThe reaction mixture was quenched with water
  5. extractionextracted with dichloromethane (4×5 ml)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customto give the crude product which
  11. customwas purified by column chromatography (10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-bb1cbfdd87664b8db2bbf673f44cec56
Source dataset
uspto-grants-2013_11
Patent number
US08592467B2

Reaction notes

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