N-methyl-2-pyrrolidone → HCID 70976811, compound

HRID 882231Notes

Reaction equation

HRID 882231 reaction equation
[NH2:1][C@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Br:12])[CH:10]=2)[N:5]([C:13](=[O:15])[CH3:14])[C@@H:4]([CH3:16])[CH2:3]1.Cl[C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][N:19]=1.CN1C(=O)CCC1.CCN(C(C)C)C(C)C>O>[Br:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]([C:13](=[O:15])[CH3:14])[C@@H:4]([CH3:16])[CH2:3][C@H:2]2[NH:1][C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][N:19]=1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 783082-Chloro-5-nitropyridineHCID 81531DiisopropylethylamineHCID 67194540cis-1-Acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine

Product 1

HCID 70976811HCID 70976811, compoundYield 161%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
200 °C

Procedure

To a flask charged with 1-((2S,4R)-4-amino-6-bromo-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (for a preparation see Intermediate 1)(2 g, 7.06 mmol) and 2-chloro-5-nitropyridine (2.240 g, 14.13 mmol) was added NMP (10 mL) and the resulting mixture treated with DIPEA (3.70 mL, 21.19 mmol). The mixture was divided between 2 flasks, each flask flushed with nitrogen, sealed and the mixture stirred under microwave irradiation at 200° C. for 2 h. The 2 reaction mixtures were combined, diluted with water and extracted with EtOAc (×4). Combined EtOAc layers were washed with water (×3) then brine, dried over MgSO4 and concentrated in vacuo. The residual brown solid was purified by chromatography eluting with an EtOAc/hexanes gradient, which gave 1-((2S,4R)-6-bromo-2-methyl-4-((5-nitropyridin-2-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)ethanone (4.6 g, 11.35 mmol, 161% yield) as a pale brown foam. LCMS (HpH, 2 min), Rt=1.08 min, MH+=405/407 (doublet).

Workup

  1. customflushed with nitrogen
  2. customsealed
  3. customThe 2 reaction mixtures
  4. extractionextracted with EtOAc (×4)
  5. washCombined EtOAc layers were washed with water (×3)
  6. dry with materialbrine, dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residual brown solid was purified by chromatography
  9. washeluting with an EtOAc/hexanes gradient, which

Sources & evidence

ORD record
ord-b848fa4cd27c48e1b76ea37718453a0b
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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