Hydrochloric Acid → HCID 78319396, compound

HRID 2280567Notes

Reaction equation

HRID 2280567 reaction equation
Cl[C:2]1[C:3]([C:12]([NH:14][C:15]2[CH:20]=[CH:19][N:18]=[C:17]([C:21]([O:23]C)=[O:22])[CH:16]=2)=[O:13])=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[F:25][C:26]([F:36])([F:35])[O:27][C:28]1[CH:33]=[CH:32][C:31]([OH:34])=[CH:30][CH:29]=1.C([O-])([O-])=O.[K+].[K+].Cl>CN1C(=O)CCC1.O>[F:25][C:26]([F:35])([F:36])[O:27][C:28]1[CH:29]=[CH:30][C:31]([O:34][C:2]2[C:3]([C:12]([NH:14][C:15]3[CH:20]=[CH:19][N:18]=[C:17]([C:21]([OH:23])=[O:22])[CH:16]=3)=[O:13])=[N:4][C:5]3[C:10]([N:11]=2)=[CH:9][CH:8]=[CH:7][CH:6]=3)=[CH:32][CH:33]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 70015p-(Trifluoromethoxy)phenolHCID 86729559HCID 86729559, compound

Product 1

HCID 78319396HCID 78319396, compoundYield 61.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of methyl 4-[(3-chloroquinoxaline-2-carbonyl)amino]pyridine-2-carboxylate (2.6 g, 7.59 mmol), 4-(trifluoromethoxy)phenol (982.5 μL, 7.59 mmol) and K2CO3 (3.14 g, 22.76 mmol) in NMP (52.00 mL) was stirred at 70° C. for two hours and at room temperature for 12 hours. 120 ml of water were added and the reaction mixture was heated to 80° C. for 60 minutes. The reaction mixture was cooled to 45° C., aqueous HCl (1.0 N) was added until a precipitate formed. This mixture was stirred for 10 minutes, and then it was filtered. The filter cake was washed with an excess of water until the pH paper showed neutral and then it was washed with an excess of hexanes. The residue was dispersed in 120 ml of ethyl acetate, stirred for 15 minutes then it was filtered. The filter cake was washed with 10 ml ethyl acetate, 10 ml dichloromethane and dried overnight to give 44344-(trifluoromethoxy)phenoxy)quinoxaline-2-carboxamido)picolinic acid (33) (2.2 g, 61%) as a light tan-colored solid. ESI-MS m/z calc. 470.08, found 471.3 (M+1)+; Retention time: 1.51 minutes (3 minutes run). 1H NMR (400 MHz, DMSO-d6) δ 11.58 (s, 1H), 8.67 (d, J=5.5 Hz, 1H), 8.51 (d, J=2.1 Hz, 1H), 8.22 (dd, J=8.4, 1.6 Hz, 1H), 7.99 (dd, J=5.5, 2.2 Hz, 1H), 7.93-7.77 (m, 3H), 7.52 (s, 4H) ppm.

Workup

  1. temperatureThe reaction mixture was cooled to 45° C.
  2. customformed
  3. filtrationit was filtered
  4. washThe filter cake was washed with an excess of water until the pH paper
  5. washit was washed with an excess of hexanes
  6. additionThe residue was dispersed in 120 ml of ethyl acetate
  7. stirringstirred for 15 minutes
  8. filtrationit was filtered
  9. washThe filter cake was washed with 10 ml ethyl acetate, 10 ml dichloromethane
  10. customdried overnight

Sources & evidence

ORD record
ord-a836428fbdce4ec7985e8aa8bf382a29
Source dataset
uspto-grants-2015_09
Patent number
US09139529B2

Reaction notes

Loading…