HCID 68756556, compound → HCID 71818810, compound

HRID 1615214Notes

Reaction equation

HRID 1615214 reaction equation
[C:1]([C:3]1[CH:11]=[C:10]2[C:6]([C:7](/[CH:12]=[CH:13]/[C:14]3[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=3)=[N:8][NH:9]2)=[CH:5][CH:4]=1)#N.CC(O)=[O:26].N1C=CC=CC=1.CN(C=O)C>O.CCOC(C)=O.[Ni]>[CH:1]([C:3]1[CH:11]=[C:10]2[C:6]([C:7](/[CH:12]=[CH:13]/[C:14]3[CH:23]=[CH:22][C:17]([C:18]([O:20][CH3:21])=[O:19])=[CH:16][CH:15]=3)=[N:8][NH:9]2)=[CH:5][CH:4]=1)=[O:26]

Participants

6

Reactant 2

HCID 68756556HCID 68756556, compoundHCID 86651947HCID 86651947, compound

Product 1

HCID 71818810HCID 71818810, compoundYield 39%

Reagents, catalysts & solvents 3

HCID 935NickelCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
55 °C

Procedure

To a mixture of (E)-methyl 4-(2-(6-cyano-1H-indazol-3-yl)vinyl)benzoate (606 mg, 2 mmol) in HOAc/pyridine/DMF (4 mL/8 mL/6 mL) was added a solution of NaH2PO2 (704 mg, 8 mmol) in H2O (4 mL), followed by Raney-Nickel 2400 (slurry in H2O, 0.4 mL). The resulting mixture was heated for 1 h at 55° C. (oil temp.). After cooling to rt, it was diluted with EtOAc (80 mL) and washed with H2O (30 mL). Aqueous layer was extracted with EtOAc (50 mL). Combined organic layers were washed with 2 N HCl (20 mL), H2O (20 mL) and dried (Na2SO4). Evaporation of solvent gave crude title compound as an orange solid which was triturated with EtOAc (10 mL), followed by suction filtration to give the title compound (240 mg, 39%) as light beige solid. The filtrate was concentrated, triturated with H2O, sonicated and the resulting precipitates were collected by suction filtration and rinsed with H2O, dried to give additional title compound (151 mg, 25%) as orange solid. 1H NMR (400 MHz, DMSO-d6) δ 13.82 (s, 1H), 10.14 (s, 1H), 8.40 (d, J=8.8 Hz, 1H), 8.18 (s, 1H), 7.97 (d, J=8.0 Hz, 2H), 7.88 (d, J=7.6 Hz, 2H), 7.77 (d, J=16.8 Hz, 1H), 7.79 (d, J=8.4 Hz, 1H), 7.64 (d, J=15.6 Hz, 1H), 3.86 (s, 3H); MS ESI 307.0 [M+H]+, calcd for [C18H14N2O3+H]+ 307.1.

Workup

  1. temperatureAfter cooling to rt
  2. washwashed with H2O (30 mL)
  3. extractionAqueous layer was extracted with EtOAc (50 mL)
  4. washCombined organic layers were washed with 2 N HCl (20 mL), H2O (20 mL)
  5. dry with materialdried (Na2SO4)
  6. customEvaporation of solvent
  7. customgave crude title compound as an orange solid which
  8. customwas triturated with EtOAc (10 mL)
  9. filtrationfollowed by suction filtration

Sources & evidence

ORD record
ord-9a8b75e10a3b46e7b9633534b36dbdd3
Source dataset
uspto-grants-2014_07
Patent number
US08765748B2

Reaction notes

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