Triethylamine → Ethyl {6-[(1-methoxy-2-phenylindolizin-3-yl)carbonyl]-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}acetate

HRID 535450Notes

Reaction equation

HRID 535450 reaction equation
ClC(Cl)(O[C:5](=[O:11])OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[CH:23]=[CH:22][C:21]([C:24]([C:26]2[N:34]3[C:29]([CH:30]=[CH:31][CH:32]=[CH:33]3)=[C:28]([O:35][CH3:36])[CH:27]=2)=[O:25])=[CH:20][C:15]=1[C:16](OC)=[O:17].[NH2:37][CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40].C(N([CH2:49][CH3:50])CC)C>O1CCOCC1.O>[CH3:36][O:35][C:28]1[C:27]([C:50]2[CH:49]=[CH:16][CH:15]=[CH:14][CH:23]=2)=[C:26]([C:24]([C:21]2[CH:20]=[C:15]3[C:14](=[CH:23][CH:22]=2)[NH:13][C:5](=[O:11])[N:37]([CH2:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])[C:16]3=[O:17])=[O:25])[N:34]2[C:29]=1[CH:30]=[CH:31][CH:32]=[CH:33]2

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 12176Glycine ethyl esterHCID 94429TriphosgeneHCID 66653221Methyl 2-amino-5-[(1-methoxyindolizin-3-yl)carbonyl]benzoate

Product 1

HCID 86683450Ethyl {6-[(1-methoxy-2-phenylindolizin-3-yl)carbonyl]-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}acetateYield 145.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

0.208 g (0.7 mmol) of triphosgene diluted in 15 ml of dioxane is added, under an inert atmosphere at ambient temperature, to 0.4 g (1 mmol) of methyl 2-amino-5-[(1-methoxyindolizin-3-yl)carbonyl]benzoate in 50 ml of dioxane. After stirring for 1 hour, 0.279 g (2 mmol) of ethyl glycinate and 0.70 ml (5 mmol) of triethylamine are added. After stirring at ambient temperature for 2 hours, the reaction medium is hydrolysed with water. After an overnight period at ambient temperature, the aqueous phase is extracted with dichloromethane. The organic phase obtained is washed with a saturated aqueous solution of sodium chloride, dried over sodium sulphate, filtered, and then concentrated under reduced pressure. The solid obtained is purified by silica gel column chromatography, elution being carried out with a dichloromethane/methanol (95/5) mixture. 0.362 g of a yellow solid is obtained.

Workup

  1. stirringAfter stirring at ambient temperature for 2 hours
  2. waitAfter an overnight period at ambient temperature
  3. extractionthe aqueous phase is extracted with dichloromethane
  4. customThe organic phase obtained
  5. washis washed with a saturated aqueous solution of sodium chloride
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe solid obtained
  10. customis purified by silica gel column chromatography, elution

Sources & evidence

ORD record
ord-46c10c3a0ec44bf3b71e0d6d2e8a56b6
Source dataset
uspto-grants-2014_10
Patent number
US08859544B2

Reaction notes

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