2,4,6-Trimethylpyridine → HCID 16073864, compound

HRID 1067990Notes

Reaction equation

HRID 1067990 reaction equation
CS(Cl)(=O)=[O:3].[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](CO)[CH:22]=3)[N:17]([CH3:28])[CH:16]=2)=[O:14])=[CH:9][CH:8]=1.[N:31]1[C:36]([CH3:37])=[CH:35][C:34]([CH3:38])=C[C:32]=1C>CN(C1C=CN=CC=1)C.CN(C=O)C>[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]([CH2:32][N:31]4[CH2:38][CH:34]5[CH2:35][CH:36]4[CH2:37][O:3]5)[CH:22]=3)[N:17]([CH3:28])[CH:16]=2)=[O:14])=[CH:9][CH:8]=1

Participants

6

Reactant 3

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

Product 1

HCID 16073864HCID 16073864, compoundYield 53%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

Methanesulfonyl chloride (0.06 mL) is added to a cold (0° C.) solution of N-(4-chlorobenzyl)-6-(hydroxymethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide (250 mg) from Preparation No. 10, DMAP (14.4 mg), and 2,4,6-collidine (0.11 mL) in anhydrous DMF (12 mL). The mixture is stirred at room temperature until the starting material is consumed. (1S, 4S)-(+)-2-Aza-5-oxabicyclo[2.2.1]heptane hydrochloride (475.9 mg) and Et3N (0.49 mL) are added to the solution. The reaction mixture is heated to 65° C. overnight. The mixture is cooled to room temperature and filtered to remove the salt that had precipitated out of solution. The filtrate is diluted with water (125 mL) to precipitate the product. The solid is adsorbed onto silica and purified by column chromatography (eluent 1% MeOH in CH2Cl2 (1 L), 2% MeOH in CH2Cl2 (1 L), 3% MeOH in CH2Cl2 (2.5 L)). Fractions homogenous by TLC are combined, concentrated, and recrystallized from CH2Cl2/hexanes to afford 164.0 mg (53%) of the title compound as a white solid.

Workup

  1. customis consumed
  2. addition(1S, 4S)-(+)-2-Aza-5-oxabicyclo[2.2.1]heptane hydrochloride (475.9 mg) and Et3N (0.49 mL) are added to the solution
  3. temperatureThe reaction mixture is heated to 65° C. overnight
  4. temperatureThe mixture is cooled to room temperature
  5. filtrationfiltered
  6. customto remove the salt that
  7. customhad precipitated out of solution
  8. additionThe filtrate is diluted with water (125 mL)
  9. customto precipitate the product
  10. custompurified by column chromatography (eluent 1% MeOH in CH2Cl2 (1 L), 2% MeOH in CH2Cl2 (1 L), 3% MeOH in CH2Cl2 (2.5 L))
  11. concentrationconcentrated
  12. customrecrystallized from CH2Cl2/hexanes

Sources & evidence

ORD record
ord-e05bfb80804143c2948e958d4d76f6e0
Source dataset
uspto-grants-2001_06
Patent number
US06248739B1

Reaction notes

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