Methanol → Methyl 1-(4-fluorophenyl)-6-methyl-1H-indazole-5-carboxylate

HRID 1748817Notes

Reaction equation

HRID 1748817 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[CH3:11])[N:7]([C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=1)[N:6]=[CH:5]2.[CH3:19][OH:20].C(N(CC)CC)C.CN([CH:31]=[O:32])C>CC([O-])=O.CC([O-])=O.[Pd+2].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[F:18][C:15]1[CH:16]=[CH:17][C:12]([N:7]2[C:8]3[C:4](=[CH:3][C:2]([C:19]([O:32][CH3:31])=[O:20])=[C:10]([CH3:11])[CH:9]=3)[CH:5]=[N:6]2)=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 670697705-bromo-1-(4-fluorophenyl)-6-methyl-1H-indazole

Product 1

HCID 67005487Methyl 1-(4-fluorophenyl)-6-methyl-1H-indazole-5-carboxylateYield 93%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst

Conditions

Temperature
90 °C

Procedure

A microwave vial was charged with 5-bromo-1-(4-fluorophenyl)-6-methyl-1H-indazole (0.29 g, 0.94 mmol), Pd(OAc)2 (0.02 g, 0.09 mmol), dppf (0.10 g, 0.19 mmol) and DMF (5.4 mL). Nitrogen was bubbled through the reaction mixture for about 10 min. The mixture was evacuated and then back-filled with CO three times. Methanol (1.9 mL, 46.9 mmol) and triethylamine (0.65 mL, 4.69 mmol) were added. The reaction mixture was heated, in a sealed microwave vessel, for about 24 h at about 90° C. After cooling to rt, the mixture was partially concentrated under reduced pressure. The residue was partitioned between EtOAc (40 mL) and water (10 mL). The organic layer was washed with brine (10 mL), dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (SiO2, EtOAc/heptane 100:0 to 0:50) to afford methyl 1-(4-fluorophenyl)-6-methyl-1H-indazole-5-carboxylate (0.25 g, 0.87 mmol, 93%). LC-MS (Table 1, Method g) Rt=2.48 min, m/z 285 (M+H)+. 1H NMR (CDCl3) δ 8.48 (s, 1H), 8.20 (s, 1H), 7.71-7.63 (m, 2H), 7.47 (s, 1H), 7.30-7.20 (m, 2H), 3.93 (s, 3H), 2.74 (s, 3H).

Workup

  1. customNitrogen was bubbled through the reaction mixture for about 10 min
  2. customThe mixture was evacuated
  3. additionback-filled with CO three times
  4. temperatureAfter cooling to rt
  5. concentrationthe mixture was partially concentrated under reduced pressure
  6. customThe residue was partitioned between EtOAc (40 mL) and water (10 mL)
  7. washThe organic layer was washed with brine (10 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by column chromatography (SiO2, EtOAc/heptane 100:0 to 0:50)

Sources & evidence

ORD record
ord-f164b46b96f64b3db517a6598c423af7
Source dataset
uspto-grants-2015_10
Patent number
US09150592B2

Reaction notes

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