Hydrogen Bromide → HCID 78319398, compound

HRID 2280578Notes

Reaction equation

HRID 2280578 reaction equation
[F:1][C:2]1[CH:21]=[CH:20][C:5]([O:6][C:7]2[C:8]([C:17]([OH:19])=O)=[N:9][C:10]3[C:15]([N:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)=[CH:4][CH:3]=1.C[O:23][C:24]1[CH:29]=[C:28]([NH2:30])[CH:27]=[CH:26][N:25]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.Br>CN1C(=O)CCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[C:8]([C:17]([NH:30][C:28]3[CH:27]=[CH:26][NH:25][C:24](=[O:23])[CH:29]=3)=[O:19])=[N:9][C:10]3[C:15]([N:16]=2)=[CH:14][CH:13]=[CH:12][CH:11]=3)=[CH:20][CH:21]=1

Participants

8

Reactant 5

HCID 260Hydrogen BromideHCID 79724-MethylmorpholineHCID 2808912-Methoxypyridin-4-amineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86729560HCID 86729560, compound

Product 1

HCID 78319398HCID 78319398, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 3-(4-fluorophenoxy)quinoxaline-2-carboxylic acid (42.6 mg, 0.15 mmol), 2-methoxypyridin-4-amine (22.3 mg, 0.18 mmol), HATU (62.7 mg, 0.16 mmol) and N-methylmorpholine (32.98 μL, 0.30 mmol) in NMP (0.5 mL) was stirred at 25° C. for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate (3×). The organics were combined, washed with water, brine, dried with Na2SO4, filtered through a short plug of silica and evaporated to dryness. The residue was taken up in HBr (0.5 mL of 33% w/v in acetic acid, 2.04 mmol) and heated at 100° C. for 4 hours. The reaction mixture was poured into water and extracted with ethyl acetate (3×). The organics were combined, evaporated and purified by reverse phase HPLC using a gradient of acetonitrile in water (1-99%) and HCl as a modifier to give 3-(4-fluorophenoxy)-N-(2-oxo-1H-pyridin-4-yl)quinoxaline-2-carboxamide (35) (5.0 mg, 9%) as a pale yellow solid. ESI-MS m/z calc. 376.10, found 377.3 (M+1)+; Retention time: 1.31 minutes (3 minutes run).

Workup

  1. extractionextracted with ethyl acetate (3×)
  2. washwashed with water, brine
  3. dry with materialdried with Na2SO4
  4. filtrationfiltered through a short plug of silica
  5. customevaporated to dryness
  6. extractionextracted with ethyl acetate (3×)
  7. customevaporated
  8. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-a84e16031bfb44a48cca1be639bd7d86
Source dataset
uspto-grants-2015_09
Patent number
US09139529B2

Reaction notes

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