Ethyl chloroformate → methyl {6-[(1-bromo-2-methylindolizin-3-yl)carbonyl]-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}acetate

HRID 1502211Notes

Reaction equation

HRID 1502211 reaction equation
Cl[C:2](OCC)=[O:3].[NH2:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([C:16]2[N:24]3[C:19]([CH:20]=[CH:21][CH:22]=[CH:23]3)=[C:18]([Br:25])[C:17]=2[CH3:26])=[O:15])=[CH:10][C:9]=1[C:27]([NH:29][CH2:30][C:31]([O:33][CH3:34])=[O:32])=[O:28]>N1C=CC=CC=1.O1CCCC1.C(OCC)(=O)C>[Br:25][C:18]1[C:17]([CH3:26])=[C:16]([C:14]([C:11]2[CH:10]=[C:9]3[C:8](=[CH:13][CH:12]=2)[NH:7][C:2](=[O:3])[N:29]([CH2:30][C:31]([O:33][CH3:34])=[O:32])[C:27]3=[O:28])=[O:15])[N:24]2[C:19]=1[CH:20]=[CH:21][CH:22]=[CH:23]2

Participants

6

Reactant 2

HCID 10928Ethyl chloroformateHCID 117776375methyl N-({2-amino-5-[(1-bromo-2-methylindolizin-3-yl)carbonyl]phenyl}carbonyl)glycinate

Product 1

HCID 89618502methyl {6-[(1-bromo-2-methylindolizin-3-yl)carbonyl]-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}acetateYield 95%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl chloroformate (1.3 mL; 13.5 mmol) is added dropwise to a solution of methyl N-({2-amino-5-[(1-bromo-2-methylindolizin-3-yl)carbonyl]phenyl}carbonyl)glycinate (2 g; 4.5 mmol) in 9 mL of pyridine at 0° C. After 15 min of stirring at ambient temperature, the reaction medium is concentrated to dryness and then diluted with ethyl acetate. The solution is washed with a 0.1 M hydrochloric acid solution and a saturated solution of sodium chloride, dried over sodium sulphate and concentrated to dryness. The yellow solid obtained is dissolved in 20 mL of anhydrous tetrahydrofuran and heated at reflux in the presence of diaza(1,3)bicyclo[5,4,0]undec-7-ene (1.35 mL; 9 mmol) for 1 h. The reaction medium is diluted with ethyl acetate, washed with a 0.1 M hydrochloric acid solution and a saturated solution of sodium chloride, dried over sodium sulphate and concentrated to dryness to give 2 g (95%) of a yellow powder.

Workup

  1. concentrationthe reaction medium is concentrated to dryness
  2. additiondiluted with ethyl acetate
  3. washThe solution is washed with a 0.1 M hydrochloric acid solution
  4. dry with materiala saturated solution of sodium chloride, dried over sodium sulphate
  5. concentrationconcentrated to dryness
  6. customThe yellow solid obtained
  7. temperatureheated
  8. washwashed with a 0.1 M hydrochloric acid solution
  9. dry with materiala saturated solution of sodium chloride, dried over sodium sulphate
  10. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-911292f8937f40cf979c4de90d3047bd
Source dataset
uspto-grants-2015_12
Patent number
US09206177B2

Reaction notes

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