3-Methylpiperidine → 2-(4-Fluorophenyl)-3-(3-methylpiperidin-1-yl)quinoxaline-6-carboxylic acid

HRID 717035Notes

Reaction equation

HRID 717035 reaction equation
Cl[C:2]1[C:3]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)=[N:4][C:5]2[C:10]([N:11]=1)=[CH:9][C:8]([C:12]([O:14]C)=[O:13])=[CH:7][CH:6]=2.[CH3:23][CH:24]1[CH2:29][CH2:28][CH2:27][NH:26][CH2:25]1>CS(C)=O>[F:22][C:19]1[CH:20]=[CH:21][C:16]([C:3]2[C:2]([N:26]3[CH2:27][CH2:28][CH2:29][CH:24]([CH3:23])[CH2:25]3)=[N:11][C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:12]([OH:14])=[O:13])[CH:9]=3)[N:4]=2)=[CH:17][CH:18]=1

Participants

4

Reactant 2

HCID 790813-MethylpiperidineHCID 77231184Methyl 3-chloro-2-(4-fluorophenyl)quinoxaline-6-carboxylate

Product 1

HCID 509914022-(4-Fluorophenyl)-3-(3-methylpiperidin-1-yl)quinoxaline-6-carboxylic acid

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
110 °C

Procedure

Into a 8-mL sealed tube, was placed methyl 3-chloro-2-(4-fluorophenyl)quinoxaline-6-carboxylate (200 mg, 0.63 mmol, 1.00 equiv), 3-methylpiperidine (313 mg, 3.16 mmol, 5.00 equiv), DMSO (3 mL). The resulting solution was stirred for overnight at 110° C. in an oil bath. The reaction was then quenched by the addition of water. The pH value of the aqueous solution was adjusted to 3-4 with 1N hydrogen chloride. The resulting solids were collected by filtration. The crude product (240 mg) was purified by Prep-HPLC under the following conditions (1#-UV1-SHIMADZU-SPD-20A): Column, SunFire Prep C18, 5 um, 19*150 mm; mobile phase, water with 0.05% TFA and CH3CN (30% CH3CN up to 100% in 8 min, hold 100% in 1.5 min, down to 30% in 1 min); Detector, Gilson UV Detector 220 nm. This resulted in 75 mg (32%) of 2-(4-fluorophenyl)-3-(3-methylpiperidin-1-yl)quinoxaline-6-carboxylic acid as a yellow solid.

Workup

  1. customInto a 8-mL sealed tube
  2. customThe reaction was then quenched by the addition of water
  3. filtrationThe resulting solids were collected by filtration
  4. customThe crude product (240 mg) was purified by Prep-HPLC under the following conditions (1#-UV1-SHIMADZU-SPD-20A)
  5. waitmobile phase, water with 0.05% TFA and CH3CN (30% CH3CN up to 100% in 8 min
  6. customin 1.5 min
  7. waitdown to 30% in 1 min)
  8. customThis resulted in 75 mg (32%) of 2-(4-fluorophenyl)-3-(3-methylpiperidin-1-yl)quinoxaline-6-carboxylic acid as a yellow solid

Sources & evidence

ORD record
ord-97266cbc44fc4b1488ad867f5aefdde2
Source dataset
uspto-grants-2015_11
Patent number
US09193693B2

Reaction notes

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