Ethyl Acetate → HCID 18404021, compound

HRID 1017634Notes

Reaction equation

HRID 1017634 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]2=[N:13][C:14]([O:18][CH2:19][C:20]3[N:21]([CH3:25])[N:22]=[CH:23][N:24]=3)=[C:15](Br)[CH:16]=[C:11]2[N:10]=[N:9]1.[S:26]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27]1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>CN(C=O)C.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]2=[N:13][C:14]([O:18][CH2:19][C:20]3[N:21]([CH3:25])[N:22]=[CH:23][N:24]=3)=[C:15]([C:28]3[CH:29]=[CH:30][S:26][CH:27]=3)[CH:16]=[C:11]2[N:10]=[N:9]1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 581760Thiophene-3-boronic acidHCID 18404041HCID 18404041, compound

Product 1

HCID 18404021HCID 18404021, compoundYield 59%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-(2-fluorophenyl)-5-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-6-bromo-1,2,3-triazolo[4,5-b]pyridine (0.10 g, 0.247 mmol) (Example 3, step c), 3-thiopheneboronic acid (0.080 g, 0.60 mmol), caesium carbonate (0.26 g, 0.80 mmol) and tetrakis(triphenylphosphine)-palladium(0) (0.03 g, 10 mol %) in DMF (4 ml) and water (1 ml) was purged with nitrogen, then heated in a sealed tube at 100° C. for 5 h. The solution was cooled, diluted with water (50 ml) and extracted with 10% methanol-dichloromethane (2×30 ml). The extracts were washed with brine (30 ml), dried (Na2SO4), filtered and concentrated. Flash column chromatography on silica gel, eluting with 4% methanol-dichloromethane, gave a brown gum that solidified on trituration with ethyl acetate. The material was recrystallised from ethyl acetate to give 3-(2-fluorophenyl)-5-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-6-(thien-3-yl)-1,2,3-triazolo[4,5-b]pyridine (0.059 g, 59%) as a beige solid, m.p. 133-135° C. (EtOAc). Found: C, 55.31; H, 3.38. C19H14N7OFS requires C, 55.40; H, 3.55%. δH (360 MHz; CDCl3) 3.73 (3H, s), 5.60 (2H, s), 7.36-7.46 (4H, m), 7.56-7.62 (1H, m), 7.66 (1H, dd, J=3 and 1), 7.71 (1H, dd, J=8 and 8), 7.86 (1H, s) and 8.46 (1H, s); m/z (ES+) 408 (M+H+).

Workup

  1. customwas purged with nitrogen
  2. temperatureThe solution was cooled
  3. additiondiluted with water (50 ml)
  4. extractionextracted with 10% methanol-dichloromethane (2×30 ml)
  5. washThe extracts were washed with brine (30 ml)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. washFlash column chromatography on silica gel, eluting with 4% methanol-dichloromethane
  10. customgave a brown gum that
  11. customThe material was recrystallised from ethyl acetate

Sources & evidence

ORD record
ord-ae2c1fbfcd2d423bbaaadb37a5d7c482
Source dataset
uspto-grants-2002_11
Patent number
US06479506B1

Reaction notes

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