Dimethylformamide → N-[(4-chlorophenyl)methyl]-1-methyl-6-(1,4-oxazepan-4-ylmethyl)-4-oxo-quinoline-3-carboxamide

HRID 1067989

Reaction equation

HRID 1067989 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]3C(=[CH:19][CH:20]=[C:21]([CH2:26]O)[CH:22]=3)N(C)C=2)=[O:14])=[CH:9][CH:8]=1.[N:31]1[C:36](C)=[CH:35][C:34](C)=[CH:33][C:32]=1C.[CH3:40][N:41]([CH:43]=O)[CH3:42]>CN(C1C=CN=CC=1)C>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:11][NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:42](=[CH:19][CH:20]=[C:21]([CH2:26][N:31]4[CH2:36][CH2:35][CH2:34][O:3][CH2:33][CH2:32]4)[CH:22]=3)[N:41]([CH3:40])[CH:43]=2)=[O:14])=[CH:29][CH:30]=1

Participants

6

Reactant 4

HCID 6228Dimethylformamide2×HCID 79532,4,6-TrimethylpyridineHCID 31297Methanesulfonyl chlorideHCID 15516933N-(4-Chlorobenzyl)-6-(hydroxymethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide

Product 1

HCID 16073862N-[(4-chlorophenyl)methyl]-1-methyl-6-(1,4-oxazepan-4-ylmethyl)-4-oxo-quinoline-3-carboxamideYield 31%

Reagents, catalysts & solvents 1

HCID 142844-(Dimethylamino)pyridineCatalyst

Procedure

Methanesulfonyl chloride (0.080 mL) is added to a cold (0° C.) solution of N-(4-chlorobenzyl)-6-(hydroxymethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide (330 mg) from Preparation No. 10, DMAP (19.1 mg), and 2,4,6-collidine (0.14 mL) in anhydrous DMF (15.7 mL). The mixture is stirred at room temperature until the starting material is consumed and a solution of 1,4-oxepane (0.963 g) from Preparation No. 33 in anhydrous DMF (3 mL) is added. The reaction mixture is heated to 56° C. for 1.5 h. The mixture is cooled to room temperature and the product is precipitated by addition of water (125 mL). The solid was adsorbed onto silica and purified by column chromatography (eluent 100% CH2Cl2 (1 L), 1% MeOH in CH2Cl2 (2 L), 1.5% MeOH in CH2Cl2 (1 L), 2% MeOH in CH2Cl2 (3 L)). Fractions homogenous by TLC are combined and concentrated to afford 124.5 mg (31%) of the title compound as a white solid.

Workup

  1. customis consumed
  2. customa solution of 1,4-oxepane (0.963 g) from Preparation No
  3. temperatureThe reaction mixture is heated to 56° C. for 1.5 h
  4. temperatureThe mixture is cooled to room temperature
  5. customthe product is precipitated by addition of water (125 mL)
  6. custompurified by column chromatography (eluent 100% CH2Cl2 (1 L), 1% MeOH in CH2Cl2 (2 L), 1.5% MeOH in CH2Cl2 (1 L), 2% MeOH in CH2Cl2 (3 L))
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-27c11d60dbcb4226807ccb1a0fc16785
Source dataset
uspto-grants-2001_06
Patent number
US06248739B1

Linked notes

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