Ethyl Acetate → (S)-6-Amino-N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-hydroxypicolinamide

HRID 509393Notes

Reaction equation

HRID 509393 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@@H:13]([C:27]2[C:32]([F:33])=[CH:31][CH:30]=[CH:29][N:28]=2)[NH:14][C:15](=[O:26])[C:16]2[CH:21]=[CH:20][C:19]([OH:22])=[C:18]([N+:23]([O-])=O)[N:17]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]([F:12])([F:11])[F:10].O.NN.CCOC(C)=O>[Ni].CO>[NH2:23][C:18]1[N:17]=[C:16]([C:15]([NH:14][C@@H:13]([C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]([F:12])([F:10])[F:11])=[C:2]([F:1])[CH:3]=2)[C:27]2[C:32]([F:33])=[CH:31][CH:30]=[CH:29][N:28]=2)=[O:26])[CH:21]=[CH:20][C:19]=1[OH:22]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 24654Hydrazine hydrate (1:1)HCID 71144193(S)-N-((3-Fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-hydroxy-6-nitropicolinamide

Product 1

HCID 71144459(S)-6-Amino-N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-hydroxypicolinamide

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 887MethanolSolvent

Conditions

Temperature
56 °C

Procedure

To a stirred suspension of Raney Nickel (0.2 g, Monarch, India) in MeOH (10 mL), was added (S)—N-((3-fluoro-4-(trifluoromethoxy)phenyl)(3-fluoropyridin-2-yl)methyl)-5-hydroxy-6-nitropicolinamide (200 mg, 0.0004252 mol) at room temperature. The temperature was raised to 56° C. and hydrazine hydrate (0.2 mL, Spectrochem, India) was added very slowly over 5 min (exothermic reaction). The reaction mixture was then stirred for 10 min at the same temperature. After completion of the reaction, monitored by TLC (TLC eluent: 50% EtOAc in petroleum ether, uv active), the mixture was cooled to room temperature, filtered through Celite® brand filter agent and concentrated under high vacuum to remove excess hydrazine hydrate. The resulting product was triturated with petroleum ether to give the title compound as a grey solid. 1H-NMR (400 MHz, DMSO-d6): δ 9.23 (d, J=8 Hz, 1H), 8.57 (d, J=4.4 Hz, 1H), 7.87 (t, J=8.8 Hz, 1H), 7.61-7.54 (m, 2H), 7.47 (d, J=11.6 Hz, 1H), 7.31 (d, J=8.4 Hz, 1H), 7.19 (d, J=8 Hz, 1H), 6.86 (d, J=8 Hz, 1H), 6.57 (d, J=8 Hz, 1H), 5.53 (br. s., 2H). MS (ESI, positive ion) m/z: 441 (M+H).

Workup

  1. custom(exothermic reaction)
  2. customAfter completion of the reaction
  3. temperaturethe mixture was cooled to room temperature
  4. filtrationfiltered through Celite® brand
  5. filtrationfilter agent
  6. concentrationconcentrated under high vacuum
  7. customto remove excess hydrazine hydrate
  8. customThe resulting product was triturated with petroleum ether

Sources & evidence

ORD record
ord-a1ce0d902bbe496dba979a3a1a442ca7
Source dataset
uspto-grants-2015_08
Patent number
US09096527B2

Reaction notes

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