2-Bromopyridine → HCID 67608577, compound

HRID 1779134Notes

Reaction equation

HRID 1779134 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:8][O:9][C:10]1[C:15](B(O)O)=[CH:14][CH:13]=[C:12]([O:19][CH3:20])[N:11]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:8][O:9][C:10]1[C:15]([C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:14][CH:13]=[C:12]([O:19][CH3:20])[N:11]=1

Participants

6

Reactant 3

HCID 79732-BromopyridineHCID 11430Potassium CarbonateHCID 2762707(2,6-Dimethoxypyridin-3-yl)boronic acid

Product 1

HCID 67608577HCID 67608577, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

2-Bromopyridine (0.475 mL, 0.78 g, 4.9 mmol) and 2,6-dimethoxy-3-pyridineboronic acid (1.09 g, 6.0 mmol, excess) were dissolved in THF (25 mL) at RT. Aqueous solution of K2CO3 (1.65 g in 10 mL of water, 12 mmol, excess) was added, followed by Pd(PPh3)4 (295 mg, 0.25 mmol). The mixture was stirred at 90° C. for 20 h under argon to give yellow solution. Organic solvent was removed under reduced pressure and the residue was extracted with dichloromethane and water. Evaporation of organic phase provided red oil that was purified by chromatography on silica gel eluting with CH2Cl2/MeOH 0 to 0.2%. The fractions containing pure product were collected, while those containing impurities were again purified by chromatography using the same conditions. After three chromatographic purifications the total yield was 965 mg (4.39 mmol; 90%) of yellow oil that crystallized as yellow solid on standing. Anal. Calcd for C12H12N2O2.0.2H2O (MW 219.84): C, 65.56; H, 5.69; N, 12.74. Found: C, 65.74; H, 5.63; N, 12.53. 1H NMR (400 MHz, CD2Cl2): 8.64 (d, J 4.0, 1H), 8.32 (d, J 8.0, 1H), 8.03 (d, J 8.0, 1H), 7.74 (t, J 8.0, 1H), 7.19 (m, 1H), 6.47 (d, J 8.0, 1H), 4.06 (s, 3H), 4.00 (s, 3H). 13C NMR (100 MHz, CD2Cl2): 163.24, 160.16, 154.36, 149.44, 142.44, 136.01, 123.97, 121.38, 114.30, 102.02, 53.75, 53.52.

Workup

  1. customto give yellow solution
  2. customOrganic solvent was removed under reduced pressure
  3. extractionthe residue was extracted with dichloromethane and water
  4. customEvaporation of organic phase
  5. customprovided red oil that
  6. customwas purified by chromatography on silica gel eluting with CH2Cl2/MeOH 0 to 0.2%
  7. additionThe fractions containing pure product
  8. customwere collected, while those containing impurities
  9. customwere again purified by chromatography
  10. customAfter three chromatographic purifications the total yield was 965 mg (4.39 mmol; 90%) of yellow oil that crystallized as yellow solid

Sources & evidence

ORD record
ord-589a05158f3f46f9a14d40c381ae79a6
Source dataset
uspto-grants-2016_02
Patent number
US09269912B2

Reaction notes

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