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

HRID 535443Notes

Reaction equation

HRID 535443 reaction equation
Cl[C:2](Cl)([O:4]C(=O)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][CH3:42])=[O:40].[CH2:43](N(CC)CC)C.C1CCN2C(=NCCC2)CC1>O1CCOCC1.O>[CH3:36][O:35][C:28]1[C:27]([CH3:43])=[C:26]([C:24]([C:21]2[CH:20]=[C:15]3[C:14](=[CH:23][CH:22]=2)[NH:13][C:2](=[O:4])[N:37]([CH2:38][C:39]([O:41][CH3:42])=[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

8

Reactant 5

HCID 8471TriethylamineHCID 69221Glycine methyl esterHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 94429TriphosgeneHCID 66653221Methyl 2-amino-5-[(1-methoxyindolizin-3-yl)carbonyl]benzoate

Product 1

HCID 66653305Methyl {6-[(1-methoxy-2-methylindolizin-3-yl)carbonyl]-2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl}acetateYield 86%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

1.22 g (4.14 mmol) of triphosgene diluted in 15 ml of dioxane are added, under an inert atmosphere at ambient temperature, to 2 g (5.91 mmol) of methyl 2-amino-5-[(1-methoxyindolizin-3-yl)carbonyl]benzoate in 65 ml of dioxane. The reaction medium is stirred for 1 hour at ambient temperature and then 1.48 g (11.82 mmol) of methyl glycinate and 4.12 ml (29.55 mmol) of triethylamine are added. The reaction medium is stirred for 18 hours and then 1.08 g (5.91 mmol) of DBU are added. After stirring for 24 hours, the medium is hydrolysed with water. The aqueous phase is extracted with dichloromethane. The organic phase obtained is washed with water, dried over sodium sulphate, filtered, and then concentrated under reduced pressure. The solid is purified by silica gel column chromatography, elution being carried out with a dichloromethane/methanol (95/5) mixture. The solid obtained is recrystallized, under hot conditions, from methanol. 1.5 g of a yellow solid are obtained.

Workup

  1. stirringThe reaction medium is stirred for 18 hours
  2. stirringAfter stirring for 24 hours
  3. extractionThe aqueous phase is extracted with dichloromethane
  4. customThe organic phase obtained
  5. washis washed with water
  6. dry with materialdried over sodium sulphate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe solid is purified by silica gel column chromatography, elution
  10. customThe solid obtained
  11. customis recrystallized, under hot conditions, from methanol

Sources & evidence

ORD record
ord-c7fd8677fb4e4edf93f40553eb53d9c5
Source dataset
uspto-grants-2014_10
Patent number
US08859544B2

Reaction notes

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