2,4,6-Trimethylpyridine → HCID 16073865, compound

HRID 1067992Notes

Reaction equation

HRID 1067992 reaction equation
CS(Cl)(=O)=O.[Cl:6][C:7]1[CH:30]=[CH:29][C:10]([CH2:11][NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([CH2:26]O)[CH:22]=3)[N:17]([CH3:28])[CH:16]=2)=[O:14])=[CH:9][CH:8]=1.N1C(C)=CC(C)=CC=1C.[O:40]1[C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=2[NH:43][CH2:42][CH2:41]1>CN(C1C=CN=CC=1)C.CN(C=O)C.C(Cl)Cl.CO.O>[Cl:6][C:7]1[CH:30]=[CH:29][C:10]([CH2:11][NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([CH2:26][N:43]4[C:44]5[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=5[O:40][CH2:41][CH2:42]4)[CH:22]=3)[N:17]([CH3:28])[CH:16]=2)=[O:14])=[CH:9][CH:8]=1

Participants

9

Reactant 4

HCID 79532,4,6-TrimethylpyridineHCID 31297Methanesulfonyl chlorideHCID 5850963,4-Dihydro-2H-1,4-benzoxazineHCID 15516933N-(4-Chlorobenzyl)-6-(hydroxymethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide

Product 1

HCID 16073865HCID 16073865, compoundYield 102.8%

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

Methanesulfonyl chloride (0.10 mL) is added to a cold (0° C.) solution of N-(4-chlorobenzyl)-6-(hydroxymethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide (0.41 g) from Preparation No. 10, DMAP (0.030 g), and 2,4,6-collidine (0.19 mL) in anhydrous DMF (15 mL). The mixture is stirred at room temperature for 12 h and then benzomorpholine (1.60 g) from above is added. The reaction mixture is stirred at room temperature for 2 h and is then heated to 65° C. overnight. The mixture is cooled to room temperature and poured water. The solid is dissolved in CH2Cl2/MeOH and adsorbed onto silica. Purification by column chromatography (eluent CH2Cl2 (1 L), 1% MeOH/CH2Cl2 (2 L)) and then recrystallization from CH2Cl2/hexanes affords 0.56 g (100%) of the title compound as a pale gold solid.

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 2 h
  2. temperatureis then heated to 65° C. overnight
  3. temperatureThe mixture is cooled to room temperature
  4. customPurification by column chromatography (eluent CH2Cl2 (1 L), 1% MeOH/CH2Cl2 (2 L))
  5. customrecrystallization from CH2Cl2/hexanes

Sources & evidence

ORD record
ord-49e83c6eb7b643b480cb1ae8f0d553c5
Source dataset
uspto-grants-2001_06
Patent number
US06248739B1

Reaction notes

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