Acetic Acid → HCID 86651946, compound

HRID 1615212Notes

Reaction equation

HRID 1615212 reaction equation
[C:1]([C:3]1[CH:11]=[C:10]2[C:6]([C:7](/[CH:12]=[CH:13]/[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[N:8][NH:9]2)=[CH:5][CH:4]=1)#N.C(O)(=[O:21])C>N1C=CC=CC=1.O.[Ni]>[CH:1]([C:3]1[CH:11]=[C:10]2[C:6]([C:7](/[CH:12]=[CH:13]/[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[N:8][NH:9]2)=[CH:5][CH:4]=1)=[O:21]

Participants

6

Reactant 2

HCID 176Acetic AcidHCID 86651945HCID 86651945, compound

Product 1

HCID 86651946HCID 86651946, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 962WaterSolvent2×HCID 1049PyridineSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of (E)-ethyl 3-(6-cyano-1H-indazol-3-yl)acrylate (723 mg, 3 mmol) in pyridine (10 mL) was added acetic acid (3 mL), followed by a solution of NaH2PO2 (1.056 g, 12 mmol) in H2O (3 mL). The resulting mixture was stirred for 0.5 min at rt before Raney-Nickel 2400 (slurry in H2O, 0.6 mL) was added in one portion. The resulting mixture was heated at 55° C. (oil temp.) for 1 h before cooling to rt. H2O (30 mL) was added and the mixture was extracted with EtOAc (50 mL×2). Combined extracts were washed with H2O (20 mL), 2 M HCl (20 mL), H2O (20 mL×2), brine (15 mL) and dried (Na2SO4). Removal of solvent gave an orange red oil which solidified upon standing O/N under high vacuum. It was then triturated with H2O (30 mL) and suction filtered, rinsed with H2O, dried to give the title compound (476 mg, 65%) as an orange red solid. 1H NMR (400 MHz, DMSO-d6) δ 14.16 (s, 1H, NH), 10.14 (s, 1H, CHO), 8.30 (d, J=8.8 Hz, 1H), 8.22 (s, 1H), 7.92 (d, J=16.4 Hz, 1H), 7.71 (d, J=7.6 Hz, 1H), 6.82 (d, J=8.4 Hz, 1H), 4.22 (q, J=6.8 Hz, 2H), 1.28 (t, J=6.8 Hz, 3H); MS ESI 245.0 [M+H]+, calcd for [C13H12N2O3+H]+ 245.1.

Workup

  1. additionwas added in one portion
  2. temperaturebefore cooling to rt
  3. extractionthe mixture was extracted with EtOAc (50 mL×2)
  4. washCombined extracts were washed with H2O (20 mL), 2 M HCl (20 mL), H2O (20 mL×2), brine (15 mL)
  5. dry with materialdried (Na2SO4)
  6. customRemoval of solvent
  7. customgave an orange red oil which
  8. customIt was then triturated with H2O (30 mL) and suction
  9. filtrationfiltered
  10. washrinsed with H2O
  11. customdried

Sources & evidence

ORD record
ord-a842719f7cc74a72a400de4bf8b4d24c
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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