Pyridinium acetate → (E)-3-(6-formyl-1H-indazol-3-yl)acrylic acid

HRID 1615286Notes

Reaction equation

[C:1]([C:3]1[CH:11]=[C:10]2[C:6]([C:7](/[CH:12]=[CH:13]/[C:14]([OH:16])=[O:15])=[N:8][NH:9]2)=[CH:5][CH:4]=1)#N.[Na].C(O)(=[O:20])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]([OH:16])=[O:15])=[N:8][NH:9]2)=[CH:5][CH:4]=1)=[O:20]

Participants

Conditions

Temperature: 55 °C

Procedure

To a solution of (E)-3-(6-cyano-1H-indazol-3-yl)acrylic acid (25 mg, 0.12 mmol) in acetic acid/pyridine (2 mL/4 mL) was added a solution of sodium hypophophite (42 mg, 0.48 mmol) in H2O (2 mL), followed by Raney-Nickel 2400 (slurry in H2O, 0.1 mL). The resulting mixture was heated at 55° C. (oil temp.) for 1 h before cooling to rt. H2O (20 mL) was added and the mixture was extracted with EtOAc (30 mL×2). The combined extracts were washed with 2M HCl (10 mL×2), H2O (10 mL×2), brine (10 mL) and dried (Na2SO4). Removal of the solvent gave the title compound (18 mg, 72%) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ 14.12 (s, 1H, NH), 12.24 (brs, 1H, CO2H), 10.01 (s, 1H, CHO), 8.26 (d, J=8.8 Hz, 1H), 8.22 (s, 1H), 7.87 (d, J=16.0 Hz, 1H), 7.71 (d, J=8.8 Hz, 1H), 6.76 (d, J=16.4 Hz, 1H); MS ESI 217.0 [M+H]+, calcd for [C11H8N2O3+H]+ 217.1.

Workup

temperaturebefore cooling to rt
extractionthe mixture was extracted with EtOAc (30 mL×2)
washThe combined extracts were washed with 2M HCl (10 mL×2), H2O (10 mL×2), brine (10 mL)
dry with materialdried (Na2SO4)
customRemoval of the solvent

Sources & evidence

ORD record: ord-c7f503476e104e2e8c41e2d1be85c08d
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08765748B2

Reaction notes

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