Propylamine → Methyl 5-({1-[3-(methoxycarbonyl)phenyl]-2-methylindolizin-3-yl}carbonyl)-2-[(propylcarbamoyl)amino]benzoate

HRID 535447Notes

Reaction equation

HRID 535447 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]([C:35]3[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([O:43][CH3:44])=[O:42])[CH:36]=3)[C:27]=2[CH3:45])=[O:25])=[CH:20][C:15]=1[C:16]([O:18][CH3:19])=[O:17].C(N(CC)CC)C.[CH2:53]([NH2:56])[CH2:54][CH3:55]>O1CCOCC1.O>[CH3:44][O:43][C:41]([C:37]1[CH:36]=[C:35]([C:28]2[C:27]([CH3:45])=[C:26]([C:24]([C:21]3[CH:22]=[CH:23][C:14]([NH:13][C:5](=[O:11])[NH:56][CH2:53][CH2:54][CH3:55])=[C:15]([CH:20]=3)[C:16]([O:18][CH3:19])=[O:17])=[O:25])[N:34]3[C:29]=2[CH:30]=[CH:31][CH:32]=[CH:33]3)[CH:40]=[CH:39][CH:38]=1)=[O:42]

Participants

7

Reactant 4

HCID 7852PropylamineHCID 8471TriethylamineHCID 94429TriphosgeneHCID 66653153Methyl 2-amino-5-({1-[3-(methoxycarbonyl)phenyl]-2-methylindolizin-3-yl}carbonyl)benzoate

Product 1

HCID 66653284Methyl 5-({1-[3-(methoxycarbonyl)phenyl]-2-methylindolizin-3-yl}carbonyl)-2-[(propylcarbamoyl)amino]benzoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent3×

Procedure

0.143 mg (0.47 mmol) of triphosgene diluted in 2 ml of dioxane are added, under an inert atmosphere at ambient temperature, to 308 mg (0.68 mmol) of methyl 2-amino-5-({1-[3-(methoxycarbonyl)phenyl]-2-methylindolizin-3-yl}carbonyl)benzoate in 5.6 ml of dioxane. The reaction medium is stirred for 2 hours at ambient temperature and then 0.28 ml (2.03 mmol) of triethylamine, and 0.11 ml (1.35 mmol) of n-propylamine diluted in 4 ml of dioxane are added. After stirring for 2 hours, the reaction medium is hydrolysed with water. The aqueous phase is extracted with dichloromethane. The organic phase obtained is washed with a 1N aqueous solution of hydrochloric acid, and then with a saturated aqueous solution of sodium chloride, dried over sodium sulphate, filtered, and 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.

Workup

  1. additionare added
  2. stirringAfter stirring for 2 hours
  3. extractionThe aqueous phase is extracted with dichloromethane
  4. customThe organic phase obtained
  5. washis washed with a 1N aqueous solution of hydrochloric acid
  6. dry with materialwith a saturated aqueous solution of sodium chloride, dried 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-732c5dbf8425404f89a76ade9c7c7ec2
Source dataset
uspto-grants-2014_10
Patent number
US08859544B2

Reaction notes

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