Acetic Acid → (E)-3-(2-(pyridin-3-yl)vinyl)-1H-indazole-6-carbaldehyde

HRID 447287Notes

Reaction equation

HRID 447287 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](/[CH:7]=[CH:8]/[C:9]2[C:17]3[C:12](=[CH:13][C:14]([C:18]#N)=[CH:15][CH:16]=3)[NH:11][N:10]=2)[CH:2]=1.CC(O)=[O:22].CN(C=O)C.[PH2]([O-])=O.[Na+]>N1C=CC=CC=1.O.[Ni]>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](/[CH:7]=[CH:8]/[C:9]2[C:17]3[C:12](=[CH:13][C:14]([CH:18]=[O:22])=[CH:15][CH:16]=3)[NH:11][N:10]=2)[CH:2]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 6228DimethylformamideHCID 66734132(E)-3-(2-(pyridin-3-yl)vinyl)-1H-indazole-6-carbonitrileHCID 178527019HCID 178527019, compound

Product 1

HCID 86651944(E)-3-(2-(pyridin-3-yl)vinyl)-1H-indazole-6-carbaldehydeYield 50%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 962WaterSolvent3×HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of (E)-3-(2-(pyridin-3-yl)vinyl)-1H-indazole-6-carbonitrile (984 mg, 3 mmol) in pyridine (30 mL) was added HOAc (8 mL), followed by DMF (30 mL). The resulting mixture was heated and sonicated to make a clear solution. After cooling to 0° C., a solution of sodium hypophosphite (1.408 g, 16 mmol) in H2O (8 mL) was added, followed by Raney-Nickel 2400 (slurry in H2O, 0.8 mL). The resulting mixture was heated at 60° C. (oil temp.) for 1 h before cooling to rt. H2O (50 mL) was added and the mixture was extracted with EtOAc (100 mL+50 mL×2). The combined extracts were dried (Na2SO4). Removal of low boiling point solvents gave a yellow solution in DMF (30 mL); H2O (500 mL) was added with swirling and a yellow precipitate formed. After standing 10 min, the resulting precipitate was collected by suction filtration, rinsed with H2O and dried under high vacuum to give the title compound (500 mg, 50%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 13.79 (s, 1H, NH), 10.14 (s, 1H, CHO), 8.90 (s, 1H), 8.48 (d, J=4.8 Hz, 1H), 8.39 (d, J=8.0 Hz, 1H), 8.19 (d, J=9.2 Hz, 1H, partially overlapping with the singlet at 8.18 ppm), 8.18 (s, 1H, partially overlapping with the doublet at 8.19 ppm), 7.75 (d, J=16.4 Hz, 1H), 7.69 (d, J=8.4 Hz, 1H), 7.59 (d, J=16.8 Hz, 1H), 7.43 (dd, J=8.0 Hz, 5.2 Hz, 1H); MS ESI 250.0 [M+H]+, calcd for [C15H11N3O+H]+ 250.1.

Workup

  1. temperatureThe resulting mixture was heated
  2. customsonicated
  3. temperatureThe resulting mixture was heated at 60° C. (oil temp.) for 1 h
  4. temperaturebefore cooling to rt
  5. extractionthe mixture was extracted with EtOAc (100 mL+50 mL×2)
  6. dry with materialThe combined extracts were dried (Na2SO4)
  7. customRemoval of low boiling point solvents
  8. customgave a yellow solution in DMF (30 mL)
  9. customa yellow precipitate formed
  10. filtrationthe resulting precipitate was collected by suction filtration
  11. washrinsed with H2O
  12. customdried under high vacuum

Sources & evidence

ORD record
ord-94ac95697b2f4b839997b368304ac318
Source dataset
uspto-grants-2013_07
Patent number
US08481533B2

Reaction notes

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