Phosgene → 2-isocyanato-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide

HRID 2234679Notes

Reaction equation

HRID 2234679 reaction equation
[NH2:1][C:2]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[C:15]3[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[O:28][CH3:29])=[CH:20][N:19]([S:30]([C:33]4[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=4)(=[O:32])=[O:31])[C:16]3=[N:17][CH:18]=2)=[CH:9][C:3]=1[C:4]([N:6]([CH3:8])[CH3:7])=[O:5].[C:40](=O)(O)[O-:41].[Na+].C(Cl)(Cl)=O>C(Cl)Cl>[N:1]([C:2]1[CH:12]=[CH:11][C:10]([C:13]2[CH:14]=[C:15]3[C:21]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[O:28][CH3:29])=[CH:20][N:19]([S:30]([C:33]4[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=4)(=[O:31])=[O:32])[C:16]3=[N:17][CH:18]=2)=[CH:9][C:3]=1[C:4]([N:6]([CH3:7])[CH3:8])=[O:5])=[C:40]=[O:41]

Participants

5

Reactant 3

HCID 6371PhosgeneHCID 516892Sodium BicarbonateHCID 597001802-amino-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide

Product 1

HCID 597002582-isocyanato-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamideYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A 50 mL round bottomed flask was charged with 2-amino-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide (500 mg, 0.926 mmol), methylene chloride (10 mL) and saturated sodium bicarbonate solution (10 mL). The solution was cooled in an ice-water bath for 5 min. Phosgene (2.5 mL, 20% w/w solution in toluene) was added to the mixture. The solution was stirred rapidly for 30 minutes. The ice-bath was removed, and the reaction mixture was stirred for an additional 30 minutes. The layers were separated and the aqueous layer was extracted twice with methylene chloride. The combined organic fractions were dried over sodium sulfate, filtered, and concentrated. The residue was triturated with anhydrous ether to give 457 mg (081 mmol, 87%) of 2-isocyanato-5-[3-(2-methoxy-phenyl)-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-N,N-dimethyl-benzamide, which was used directly without any further purification or characterization in the subsequent step.

Workup

  1. temperatureThe solution was cooled in an ice-water bath for 5 min
  2. customThe ice-bath was removed
  3. stirringthe reaction mixture was stirred for an additional 30 minutes
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted twice with methylene chloride
  6. dry with materialThe combined organic fractions were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was triturated with anhydrous ether

Sources & evidence

ORD record
ord-addcda731459495ab4144a295395f865
Source dataset
uspto-grants-2010_05
Patent number
US07709645B2

Reaction notes

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