Triphosgene → 3-[1-(3,5-Dimethyl-1h-pyrrol-2-yl)-meth-(z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carbonyl chloride

HRID 1008110Notes

Reaction equation

HRID 1008110 reaction equation
ClC(Cl)(OC(=O)[O:6][C:7]([Cl:10])(Cl)Cl)Cl.[CH3:13][C:14]1[CH:18]=[C:17]([CH3:19])[NH:16][C:15]=1/[CH:20]=[C:21]1\[C:22](=[O:30])[NH:23][C:24]2[C:29]\1=[CH:28][CH:27]=[CH:26][CH:25]=2>C1COCC1>[CH3:13][C:14]1[CH:18]=[C:17]([CH3:19])[NH:16][C:15]=1/[CH:20]=[C:21]1\[C:22](=[O:30])[N:23]([C:7]([Cl:10])=[O:6])[C:24]2[C:29]\1=[CH:28][CH:27]=[CH:26][CH:25]=2

Participants

4

Reactant 2

HCID 94429TriphosgeneHCID 5329098Semaxanib

Product 1

HCID 879046953-[1-(3,5-Dimethyl-1h-pyrrol-2-yl)-meth-(z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carbonyl chlorideYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To the solution of triphosgene (7.2 gram, 24.2 mmol) in 500 mL of anhydrous THF was added 56 mL of thiethylamine in one portion and the resulting mixture was stirred at room temperature for 10 minutes. Solid 3-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole (5.768 gram, 24.2 mmol) was added in one portion to the above mixture. The reaction mixture was stirred at room temperature for 1 h and then cooled on ice bath to 0-4° C. Ice-cold 4M HCl aq. (1.5 L) was added in one portion upon vigorous stirring. The resulting suspension was further stirred for 10 min., and filtered. The solid was washed with ice-cold 4M HCl aq. and dried on the high vacuum oven overnight. The crude product was recrystallized from anhydrous benzene and filtered. The solid was then washed with cyclohexane and dried in a vacuum oven overnight to yield 3-[1-(3,5-dimethyl-1H-pyrrol-2-yl)-meth-(Z)-ylidene]-2-oxo-2,3-dihydro-indole-1-carbonyl chloride (5.531 gram, 76%). 1HNMR (400 MHz, DMSO-d6) δ 12.41 (s, br, 1H), 7.98 (m, 1H), 7.52 (m, 1H), 7.43 (s, 1H), 7.25 (m, 1H), 6.08 (d, br, J=2 Hz, 1H), 2.43 (s, 3H), 2.36 (s, 3H).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 1 h
  2. temperaturecooled on ice bath to 0-4° C
  3. stirringThe resulting suspension was further stirred for 10 min.
  4. filtrationfiltered
  5. washThe solid was washed with ice-cold 4M HCl aq.
  6. customdried on the high vacuum oven overnight
  7. customThe crude product was recrystallized from anhydrous benzene
  8. filtrationfiltered
  9. washThe solid was then washed with cyclohexane
  10. customdried in a vacuum oven overnight

Sources & evidence

ORD record
ord-f78c771117c74fbdac0d0f9af7375cd2
Source dataset
uspto-grants-2004_09
Patent number
US06797725B2

Reaction notes

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