1,1'-Carbonyldiimidazole → 3-{1-(1,3-Benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonamido]-2-oxoethyl}-6-(methoxycarbonyl)-1-methyl-1h-indole

HRID 322090Notes

Reaction equation

HRID 322090 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[O:13]1[C:17]2[CH:18]=[CH:19][C:20]([CH:22]([C:26]3[C:34]4[C:29](=[CH:30][C:31]([C:35]([O:37][CH3:38])=[O:36])=[CH:32][CH:33]=4)[N:28]([CH3:39])[CH:27]=3)[C:23](O)=[O:24])=[CH:21][C:16]=2[O:15][CH2:14]1.[CH3:40][O:41][C:42]1[CH:47]=[C:46]([CH3:48])[CH:45]=[CH:44][C:43]=1[S:49]([NH2:52])(=[O:51])=[O:50].N12CCCN=C1CCCCC2>O1CCCC1>[O:13]1[C:17]2[CH:18]=[CH:19][C:20]([CH:22]([C:26]3[C:34]4[C:29](=[CH:30][C:31]([C:35]([O:37][CH3:38])=[O:36])=[CH:32][CH:33]=4)[N:28]([CH3:39])[CH:27]=3)[C:23]([NH:52][S:49]([C:43]3[CH:44]=[CH:45][C:46]([CH3:48])=[CH:47][C:42]=3[O:41][CH3:40])(=[O:50])=[O:51])=[O:24])=[CH:21][C:16]=2[O:15][CH2:14]1

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 50933692-Methoxy-4-methylbenzenesulfonamideHCID 220099412-(1,3-Benzodioxol-5-yl)-2-(6-methoxycarbonyl-1-methyl-1H-indol-3-yl)acetic acid

Product 1

HCID 224672003-{1-(1,3-Benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonamido]-2-oxoethyl}-6-(methoxycarbonyl)-1-methyl-1h-indoleYield 71.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1,1′-Carbonyldiimidazole (2.8 kg) was added to a stirred solution of 2-(1,3-benzodioxol-5-yl)-2-(6-methoxycarbonyl-1-methyl-1H-indol-3-yl)acetic acid (from step (a), 5.0 kg) in dry tetrahydrofuran (50 liters) at room temperature under a nitrogen atmosphere. The suspension was heated to reflux for 1.5 h, allowed to cool to room temperature, and treated sequentially with 2-methoxy-4-methylbenzenesulfonamide (see Preparation 11, International Patent Application WO 97/43260; 3.0 kg) and 1,8-diazabicyclo[5.4.0]undec-7-ene (2.3 kg). The mixture was heated to reflux for 3.5 h, allowed to cool to room temperature and quenched by the addition of 2M hydrochloric acid (40 liters). The product was extracted from the acidic aqueous solution with dichloromethane (40 liters) and the organic phase was washed with 2M hydrochloric acid (40 liters) and water (40 liters). The organic phase was concentrated to low volume, diluted with acetonitrile (93 liters) and the resulting suspension heated to reflux. The mixture was allowed to cool and the precipitated product collected by filtration to give the subtitle compound as a white crystalline solid (5.34 kg, 71.3%).

Workup

  1. temperatureThe suspension was heated
  2. temperatureto reflux for 1.5 h
  3. temperatureThe mixture was heated
  4. temperatureto reflux for 3.5 h
  5. temperatureto cool to room temperature
  6. customquenched by the addition of 2M hydrochloric acid (40 liters)
  7. extractionThe product was extracted from the acidic aqueous solution with dichloromethane (40 liters)
  8. washthe organic phase was washed with 2M hydrochloric acid (40 liters) and water (40 liters)
  9. concentrationThe organic phase was concentrated to low volume
  10. additiondiluted with acetonitrile (93 liters)
  11. temperaturethe resulting suspension heated to reflux
  12. temperatureto cool
  13. filtrationthe precipitated product collected by filtration

Sources & evidence

ORD record
ord-ed821e159ea049039d2d2d20958646f2
Source dataset
uspto-grants-2001_04
Patent number
US06211223B1

Reaction notes

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