Cesium carbonate → HCID 71571665, compound

HRID 1777783Notes

Reaction equation

HRID 1777783 reaction equation
Br[C:2]1[N:7]2[C:8](=[O:23])[N:9]([CH2:11][CH2:12][C:13]3[CH:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[N:14]=3)[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.[N:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=O.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C>[N:24]1[CH:29]=[CH:28][C:27]([C:2]2[N:7]3[C:8](=[O:23])[N:9]([CH2:11][CH2:12][C:13]4[CH:22]=[CH:21][C:20]5[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=5)[N:14]=4)[N:10]=[C:6]3[CH:5]=[CH:4][CH:3]=2)=[CH:26][CH:25]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 71573383HCID 71573383, compound

Product 1

HCID 71571665HCID 71571665, compoundYield 20%

Reagents, catalysts & solvents 3

HCID 178418851HCID 178418851, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Triazolopyridinone 2-4 (40 mg, 0.11 mmol) and pyridin-4-ylboronic acid (27 mg, 0.22 mmol) were placed in a microwave vial and dissolved in dioxane (1 mL). To the mixture was added 1 M aq. Cs2CO3 solution (0.22 mL, 0.22 mmol). The mixture was then sparged with N2 gas for 3 min, and bis(tri-tert-butylphosphine)palladium (5.5 mg, 0.011 mmol) was added. The vial was capped and heated at 100° C. under microwave irradiation for 30 min. After cooling, the reaction mixture was diluted with EtOAc (100 mL), washed with water (30 mL) and brine (30 mL), dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (12 g cartridge), eluting with 0-10% MeOH/CH2Cl2. The fractions containing the desired product (5-1) were pooled, and after solvent removal in vacuo, 8.0 mg (20%) of a yellow solid were obtained. 1H NMR (400 MHz, CHCl3-d): δ 8.63 (dd, J=4.9, 1.5 Hz, 2H), 8.07 (d, J=8.4 Hz, 1H), 7.99 (d, J=8.4 Hz, 1H), 7.79 (d, J=8.0 Hz, 1H), 7.68 (ddd, J=8.4, 6.8, 1.6 Hz, 1H), 7.53-7.48 (m, 1H), 7.31 (d, J=8.4 Hz, 1H), 7.26 (d, J=6.0 Hz, 2H), 7.16 (d, J=9.6 Hz, 1H), 7.08 (dd, J=9.6, 6.4 Hz, 1H), 6.36 (d, J=6.4 Hz, 1H), 4.49 (t, J=7.2 Hz, 2H), 3.51 (t, J=7.2 Hz, 2H). HRMS (ES) 368.1508 (M+H) found, 368.1509 required.

Workup

  1. customThe mixture was then sparged with N2 gas for 3 min
  2. customThe vial was capped
  3. temperatureAfter cooling
  4. washwashed with water (30 mL) and brine (30 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel flash column chromatography (12 g cartridge)
  9. washeluting with 0-10% MeOH/CH2Cl2
  10. additionThe fractions containing the desired product (5-1)
  11. customafter solvent removal in vacuo

Sources & evidence

ORD record
ord-11db43d272db48a2b02df48929a9a25e
Source dataset
uspto-grants-2016_02
Patent number
US09266881B2

Reaction notes

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