Cesium carbonate → HCID 67514197, compound

HRID 1508535Notes

Reaction equation

HRID 1508535 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1B(O)O.Br[C:14]1[C:15]([CH3:24])=[CH:16][C:17]([C:20]([O:22][CH3:23])=[O:21])=[N:18][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:14]1[C:15]([CH3:24])=[CH:16][C:17]([C:20]([O:22][CH3:23])=[O:21])=[N:18][CH:19]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 15789384(2-Fluoro-4-methoxyphenyl)boronic acidHCID 56763836Methyl 5-bromo-4-methylpyridine-2-carboxylate

Product 1

HCID 67514197HCID 67514197, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(2-Fluoro-4-methoxyphenyl)boronic acid (177 mg, 1.043 mmol), methyl 5-bromo-4-methylpyridine-2-carboxylate (200 mg, 0.869 mmol), 1,1bis(di-tert-butylphosphino)ferrocene palladium dichloride (89 mg, 0.130 mmol), cesium carbonate (623 mg, 1.913 mmol) and THF (5 mL) were sealed in a microwave vessel and subject to microwave irradiation at 140° C. for 20 min. The reaction crude was combined with the crude from an identical probe reaction (44.3 mg scale). Volatiles were removed under reduced pressure. The resulting pot residue was purified by preparative HPLC (reverse phase, Kromasil® 100-5C18, 100×21.1 mm) eluting with acetonitrile/water+0.1% TFA (30% to 100% organic in 10 min, then to 100% for 2 min, 20 mL/min). Related fractions were pooled and evaporated under reduced pressure to afford a dark solid. This solid was further purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 50 g cartridge). The column was eluted with an EtOAc/hexanes mixture (0% to 100%). Related fractions were pooled and evaporated to afford a light yellow oil as the titled compound. LCMS calc.=275.10. found=276.11 (M+H)+.

Workup

  1. customsubject to microwave irradiation at 140° C. for 20 min
  2. customThe reaction crude
  3. customwas combined with the crude from an identical probe reaction (44.3 mg scale)
  4. customVolatiles were removed under reduced pressure
  5. customThe resulting pot residue was purified by preparative HPLC (reverse phase, Kromasil® 100-5C18, 100×21.1 mm)
  6. washeluting with acetonitrile/water+0.1% TFA (30% to 100% organic in 10 min
  7. customevaporated under reduced pressure
  8. customto afford a dark solid
  9. customThis solid was further purified by flash chromatography (SiO2, Biotage SNAP Cartridge, silica gel, KP-Sil, 50 g cartridge)
  10. washThe column was eluted with an EtOAc/hexanes mixture (0% to 100%)
  11. customevaporated

Sources & evidence

ORD record
ord-6af94e81e12349988a87a1a31673b92f
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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