Hydrochloric Acid → 9-Bromo-5-methylsulfonyloxymethyl-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dione

HRID 52492Notes

Reaction equation

HRID 52492 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[CH2:16][CH2:15][CH:14]([CH2:17][OH:18])[N:6]3[C:7](=[O:13])[C:8](=[O:12])[NH:9][C:10]([CH:11]=1)=[C:5]23.C(N(CC)CC)C.[CH3:26][S:27](Cl)(=[O:29])=[O:28].Cl>C1COCC1.O>[Br:1][C:2]1[CH:3]=[C:4]2[CH2:16][CH2:15][CH:14]([CH2:17][O:18][S:27]([CH3:26])(=[O:29])=[O:28])[N:6]3[C:7](=[O:13])[C:8](=[O:12])[NH:9][C:10]([CH:11]=1)=[C:5]23

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471Triethylamine2×HCID 31297Methanesulfonyl chloride2×HCID 544705519-bromo-5-hydroxymethyl-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dione

Product 1

HCID 542445079-Bromo-5-methylsulfonyloxymethyl-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dioneYield 64.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 9-bromo-5-hydroxymethyl-6,7-dihydro-1H, 5H-pyrido[1,2,3-de]quinoxaline-2,3-dione (3 g, 9.65 mmol) and triethylamine (1,28 g, 12.67 mmol) in THF (200 mL) was added methanesulfonyl chloride (1.44 g, 12.57 mmol) at -20° C. The mixture was stirred for 1.5 h at the same temperature and triethylamine (0.6 mL) and methanesulfonylchloride (0.4 mL) were added. The mixture was further stirred for 1 h at -20° C. and for 30 min at 0° C. and poured into water (500 mL). The mixture was acidified with 3N hydrochloric acid and extracted with ethyl acetate (500 mL×3). The organic layers were washed with brine, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel column chromatography with 1 to 5% acetic acid/ethyl acetate to give 2.42 g of the title compound (64%): mp 125°~130° C. (dec); 1H NMR (270 MHz, DMSO-d6) δ12.05 (bs, 1H), 7.20 (s, 1H), 7.15 (s, 1H), 4.97~5.06 (m, 1H), 4.28 (d, 2H, J=7.5 Hz), 3.20 (s, 3H), 2.97 (ddd, 1H, J=17.1, 13.5, 4.5 Hz), 2.83 (dm, 1H, J=17.1 Hz), 2.27 (dm, 1H, J=13.5 Hz), 1.81~1.97 (m, 1H).

Workup

  1. additionwere added
  2. extractionextracted with ethyl acetate (500 mL×3)
  3. washThe organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel column chromatography with 1 to 5% acetic acid/ethyl acetate

Sources & evidence

ORD record
ord-f433db8583554be0848832a7b04a78c8
Source dataset
uspto-grants-1997_04
Patent number
US05616586

Reaction notes

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