Potassium Carbonate → HCID 178461424, compound

HRID 2047510Notes

Reaction equation

HRID 2047510 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:5]2[N:6]=[C:7]([C@H:9]3[CH2:12][C@H:11]([N:13]4[CH2:17][CH2:16][CH2:15][C@H:14]4[CH3:18])[CH2:10]3)[S:8][C:4]=2[CH:3]=1.[N:21]1[CH:26]=[C:25](B(O)O)[CH:24]=[N:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)(C)C.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>[CH3:18][C@@H:14]1[CH2:15][CH2:16][CH2:17][N:13]1[C@H:11]1[CH2:12][C@H:9]([C:7]2[S:8][C:4]3[CH:3]=[C:2]([C:25]4[CH:26]=[N:21][CH:22]=[N:23][CH:24]=4)[CH:20]=[CH:19][C:5]=3[N:6]=2)[CH2:10]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 178461421HCID 178461421, compound

Product 1

HCID 178461424HCID 178461424, compoundYield 82.6%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 3776IsopropanolSolvent

Procedure

A solution of the product of Example 1E (40 mg, 0.114 mmole), pyrimidine-5-boronic acid (CAS #109299-78-7) (21 mg, 0.169 mmole), dichlorobis(triphenylphosphine)palladium(II) (8 mg, 0.01 mmole) and potassium carbonate (47 mg, 0.34 mmole) in 1 ml isopropanol was heated at 85° C. overnight with stirring. The reaction was then quenched with water and extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by column chromatography (eluted by 0.35% ammonium hydroxide and 3.5% methanol in dichloromethane) to give 33 mg (82% yield) of title compound. 1H NMR (400 MHz, CDCl3) δ ppm 9.23 (s, 1H), 9.02 (s, 2H), 8.12 (d, J=8.59 Hz, 1H), 8.06 (d, J=1.84 Hz, 1H), 7.67 (dd, J=8.44, 1.99 Hz, 1H), 3.83-3.94 (m, 1H), 3.46-3.62 (m, 1H), 2.99-3.14 (m, 1H), 2.64-2.85 (m, 3H), 2.43-2.64 (m, 2H), 2.23-2.40 (m, 1H), 1.89-2.03 (m, 1H), 1.78-1.91 (m, 1H), 1.67-1.78 (m, 1H), 1.42-1.56 (m, 1H), 1.14 (d, J=4.91 Hz, 3H). MS: (M+H)+=351.

Workup

  1. customThe reaction was then quenched with water
  2. extractionextracted three times with dichloromethane
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (eluted by 0.35% ammonium hydroxide and 3.5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-fbbd8a1e61b9449dbd3e869e7117069f
Source dataset
uspto-grants-2013_11
Patent number
US08592467B2

Reaction notes

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