O-Toluidine → HCID 66926890, compound

HRID 81049Notes

Reaction equation

HRID 81049 reaction equation
[Cl:1][C:2]1[C:9](F)=[N:8][CH:7]=[C:6]([Cl:11])[C:3]=1[C:4]#[N:5].[NH2:12][C:13]1[C:14]([CH3:19])=[CH:15][CH:16]=[CH:17][CH:18]=1>C(OCC)(=O)C>[Cl:1][C:2]1[C:9]([NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])=[N:8][CH:7]=[C:6]([Cl:11])[C:3]=1[C:4]#[N:5]

Participants

4

Reactant 2

HCID 7242O-ToluidineHCID 669269313,5-Dichloro-2-fluoroisonicotinonitrile

Product 1

HCID 66926890HCID 66926890, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 3,5-dichloro-2-fluoroisonicotinonitrile (1.00 g, 5.24 mmol) and o-toluidine (10 g, 93 mmol) was heated to 150° C. for 20 h. After cooling to room temperature, the mixture was diluted with ethyl acetate (200 mL), washed with 1 N HCl (2×20 mL), saturated sodium bicarbonate (20 mL), and brine (20 mL), dried (MgSO4) and concentrated. Silica gel chromatography, loading with dichloromethane-hexanes (1:1) and eluting with 0 to 20% ethyl acetate in hexanes, gave 3,5-dichloro-2-(o-tolylamino)isonicotinonitrile as yellow solid (1.10 g, 76% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.18 (1H, s), 7.71 (1H, δ, J=7.78 Hz), 7.23-7.40 (2H, m), 7.01-7.13 (1H, m), 6.70-6.94 (1H, m), 2.29 (3H, s); MS (ES+) m/z: 278 (M+H); LC retention time: 3.68 min (analytical HPLC Method A).

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with 1 N HCl (2×20 mL), saturated sodium bicarbonate (20 mL), and brine (20 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. washeluting with 0 to 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-939440811bd4423e97d5cea710264512
Source dataset
uspto-grants-2014_09
Patent number
US08846673B2

Reaction notes

Loading…