Benzene → 2-Methoxy-3-(6-methoxypyridin-2-yl)-5-(1H-1,2,4-triazol-1-ylmethyl)pyridine

HRID 2271472Notes

Reaction equation

HRID 2271472 reaction equation
[N:1]1([CH2:6][C:7]2[CH:8]=[C:9](Br)[C:10]([O:13][CH:14](F)F)=[N:11][CH:12]=2)[CH:5]=[N:4][CH:3]=[N:2]1.[CH3:18][O:19][C:20]1[N:25]=[C:24](B(O)O)[CH:23]=[CH:22][CH:21]=1.C1C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>CCO.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>[CH3:14][O:13][C:10]1[C:9]([C:24]2[CH:23]=[CH:22][CH:21]=[C:20]([O:19][CH3:18])[N:25]=2)=[CH:8][C:7]([CH2:6][N:1]2[CH:5]=[N:4][CH:3]=[N:2]2)=[CH:12][N:11]=1

Participants

7

Reactant 4

HCID 241BenzeneHCID 10340Sodium CarbonateHCID 27627416-Methoxypyridine-2-boronic acidHCID 904149845-((1H-1,2,4-Triazol-1-yl)methyl)-3-bromo-2-(difluoromethoxy)pyridine2×

Product 1

HCID 863038032-Methoxy-3-(6-methoxypyridin-2-yl)-5-(1H-1,2,4-triazol-1-ylmethyl)pyridineYield 25%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 5-((1H-1,2,4-triazol-1-yl)methyl)-3-bromo-2-(difluoromethoxy)pyridine (Intermediate 13, 50 mg, 0.16 mmol), (6-methoxypyridin-2-yl)boronic acid (46 mg, 0.30 mmol), in EtOH (2.45 mL), benzene (7.00 mL), was combined with tetrakis(triphenylphosphine)palladium(0) (27 mg, 0.02 mmol), and 4 M aqueous sodium carbonate (3 mL) in a microwave vial. The vial was sealed, purged with nitrogen and heated under microwave conditions to 120° C. for 12 minutes. Water was removed from the reaction with a pipette, and the crude reaction mix was filtered thru CELITE®, and washed with EtOAc (3×5 mL). The combined organic layers were dried (Na2SO4), and the solvent was removed under reduced pressure. Purification (FCC, SiO2, 30-70% EtOAc/hexanes) afforded the title compound (11.9 mg, 25%). 1H NMR (400 MHz, DMSO-d6) δ 7.88 (s, 1H), 7.58 (d, J=2.7 Hz, 1H), 7.41 (d, J=2.3 Hz, 1H), 7.24 (s, 1H), 6.91-6.84 (m, 2H), 5.93 (d, J=4.3 Hz, 1H), 4.69 (s, 2H), 3.97 (s, 3H), 3.14 (s, 3H). [M+H]=298.02.

Workup

  1. customThe vial was sealed
  2. custompurged with nitrogen
  3. customWater was removed from the reaction with a pipette
  4. customthe crude reaction
  5. additionmix
  6. filtrationwas filtered thru CELITE®
  7. washwashed with EtOAc (3×5 mL)
  8. dry with materialThe combined organic layers were dried (Na2SO4)
  9. customthe solvent was removed under reduced pressure
  10. customPurification (FCC, SiO2, 30-70% EtOAc/hexanes)

Sources & evidence

ORD record
ord-ad9de2898c59442b84fb8946a6cb9843
Source dataset
uspto-grants-2015_09
Patent number
US09120770B2

Reaction notes

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