Methanol → 3-(Azepan-1-yl)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid

HRID 1405594Notes

Reaction equation

HRID 1405594 reaction equation
[N:1]1([C:8]2[C:9]([C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)=[N:10][C:11]3[C:16]([N:17]=2)=[CH:15][C:14]([C:18]([O:20]CCCC)=[O:19])=[CH:13][CH:12]=3)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.CO.[OH-].[Na+]>O>[N:1]1([C:8]2[C:9]([C:25]3[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=3)=[N:10][C:11]3[C:16]([N:17]=2)=[CH:15][C:14]([C:18]([OH:20])=[O:19])=[CH:13][CH:12]=3)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 67042167Butyl 3-(azepan-1-yl)-2-(4-fluorophenyl)quinoxaline-6-carboxylate

Product 1

HCID 509913103-(Azepan-1-yl)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
50 °C

Procedure

Into a 50-mL round-bottom flask, was placed butyl 3-(azepan-1-yl)-2-(4-fluorophenyl)quinoxaline-6-carboxylate (150 mg, 0.36 mmol, 1.00 equiv), methanol (15 mL), sodium hydroxide (71 mg, 1.77 mmol, 4.98 equiv), water (2 mL). The resulting solution was stirred for 2 hrs at 50° C. in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 20 mL of H2O. The pH value of the aqueous solution was adjusted to 4-5 with aq hydrogen chloride (1 mol/L). The resulting solids were collected by filtration. The crude product (150 mg) was purified by Prep-HPLC with the following conditions (1#-Waters 2767-1): Column, XbridgePrep Shield RP 18, 5 um, 19*150 mm; mobile phase, water with 0.05% TFA and CH3CN (60% CH3CN up to 90% in 8 min, up to 100% in 1.5 min); Detector, UV 220 254 nm. This resulted in 80 mg (61%) of 3-(azepan-1-yl)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid as a yellow solid.

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. additionThe resulting solution was diluted with 20 mL of H2O
  4. filtrationThe resulting solids were collected by filtration
  5. customThe crude product (150 mg) was purified by Prep-HPLC with the following conditions (1#-Waters 2767-1)
  6. waitmobile phase, water with 0.05% TFA and CH3CN (60% CH3CN up to 90% in 8 min
  7. waitup to 100% in 1.5 min)
  8. customThis resulted in 80 mg (61%) of 3-(azepan-1-yl)-2-(4-fluorophenyl)quinoxaline-6-carboxylic acid as a yellow solid

Sources & evidence

ORD record
ord-678e820732074aaead31cb778d590706
Source dataset
uspto-grants-2014_12
Patent number
US08916560B2

Reaction notes

Loading…