Methanesulfonic Acid → Pranlukast Chromene Carboxamide Impurity

HRID 2258282Notes

Reaction equation

HRID 2258282 reaction equation
C(C1C=CC(C)=[N:7]C=1)C.[C:10]1([CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]2[CH:45]=[CH:44][C:24]([C:25]([NH:27][C:28]3[C:37]4[O:36][C:35]([C:38](OCC)=[O:39])=[CH:34][C:33](=[O:43])[C:32]=4[CH:31]=[CH:30][CH:29]=3)=[O:26])=[CH:23][CH:22]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CS(O)(=O)=O>CO>[C:10]1([CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]2[CH:45]=[CH:44][C:24]([C:25]([NH:27][C:28]3[C:37]4[O:36][C:35]([C:38](=[O:39])[NH2:7])=[CH:34][C:33](=[O:43])[C:32]=4[CH:31]=[CH:30][CH:29]=3)=[O:26])=[CH:23][CH:22]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 6395Methanesulfonic AcidHCID 77285-Ethyl-2-methylpyridineHCID 113407088-[4-(4-phenyl-1-butoxy)benzoyl]amino-2-ethoxycarbonyl-4-oxo-4H-benzopyran

Product 1

HCID 10895736Pranlukast Chromene Carboxamide ImpurityYield 99%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
80 °C

Procedure

To a mixture containing 120 ml of 5-ethyl-2-methylpyridine and 75 ml of methanol was added 29.5 g of 8-[4-(4-phenyl-1-butoxy)benzoyl]amino-2-ethoxycarbonyl-4-oxo-4H-benzopyran, into which 8.2 g of ammonia gas was bubbled around 0° C., and the mixture was stirred below 30° C. for 3 hours. Then, the temperature was increased to 80° C., and excess ammonia and part of the methanol were removed and recovered into methanol in another vessel. The recovered ammonia and/or methanol can be used again in the subsequent production. The temperature was increased to 80° C., and the remaining methanol and part of 5-ethyl-2-methylpyridine were removed by reducing a pressure down to 30 mmHg. Subsequently, 60.8 mmol (5.84 g) of methane sulfonic acid was added, and the mixture was stirred at 100° C. for 6 hours. Then, the temperature was decreased to 60° C., and methanol was added dropwise at 50° to 60° C. The mixture Was cooled to 0° C., and the deposited crystals were collected by filtration, which afforded 27.7 g of 8-[4-(4-phenyl-1-butoxy)benzoyl]amino-2-carbamoyl-4-oxo-4H-benzopyran (yield 99%).

Workup

  1. custominto which 8.2 g of ammonia gas was bubbled around 0° C.
  2. customexcess ammonia and part of the methanol were removed
  3. customrecovered into methanol in another vessel
  4. temperatureThe temperature was increased to 80° C.
  5. customthe remaining methanol and part of 5-ethyl-2-methylpyridine were removed
  6. stirringthe mixture was stirred at 100° C. for 6 hours
  7. customwas decreased to 60° C.
  8. temperatureThe mixture Was cooled to 0° C.
  9. filtrationthe deposited crystals were collected by filtration, which

Sources & evidence

ORD record
ord-5729695d0aa046f794cf30f61de54269
Source dataset
uspto-grants-1997_08
Patent number
US05659051

Reaction notes

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