Sodium hydride → HCID 10128455, compound

HRID 1358929Notes

Reaction equation

HRID 1358929 reaction equation
[CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([NH:12][C:13]([C:15]3[CH:20]=[CH:19][NH:18][C:17](=[O:21])[CH:16]=3)=[O:14])[S:11][C:7]=2[C:6]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:5][CH:4]=1.[H-].[Na+].[Br-].[Li+].Cl[CH2:33][C:34]([N:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1)=[O:35]>CN(C=O)C.COCCOC.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([NH:12][C:13]([C:15]3[CH:20]=[CH:19][N:18]([CH2:33][C:34]([N:36]4[CH2:41][CH2:40][O:39][CH2:38][CH2:37]4)=[O:35])[C:17](=[O:21])[CH:16]=3)=[O:14])[S:11][C:7]=2[C:6]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 74040Morpholine, 4-(chloroacetyl)-HCID 82050Lithium BromideHCID 11361168HCID 11361168, compound

Product 1

HCID 10128455HCID 10128455, compoundYield 31.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of 200 mg (0.52 mmol) 2-oxo-1,2-dihydro-pyridine-4-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide in 1 ml DMF and 4 ml 1,2-dimethoxyethane was added 44 mg (1.04 mmol) sodium hydride (60% dispersion in mineral oil). After stirring for 15 min at room temperature, 90 mg (1.04 mmol) lithium bromide was added and stirring continued for a further 15 min. 95 mg (0.58 mmol) 4-(2-chloroacetyl)morpholine was then added and the mixture was stirred at room temperature for 16 h. The reaction mixture was then diluted with ethyl acetate, and washed sequentially with 0.5 M hydrochloric acid, saturated sodium bicarbonate solution and saturated brine. The combined aqueous phases were filtered, and the filter cake washed with ether, then resuspended in toluene and concentrated in vacuo. Flash chromatography (MeOH/CH2Cl2) followed by trituration in ethyl acetate afforded 83 mg (31%) 1-(2-morpholin-4-yl-2-oxo-ethyl)-2-oxo-1,2-dihydro-pyridine-4-carboxylic acid (4-methoxy-7-morpholin-4-yl-benzothiazol-2-yl)-amide as a yellow crystalline solid. ES-MS m/e (%): 536 (M+Na+, 25), 514 (M+H+, 100).

Workup

  1. stirringstirring
  2. waitcontinued for a further 15 min
  3. stirringthe mixture was stirred at room temperature for 16 h
  4. washwashed sequentially with 0.5 M hydrochloric acid, saturated sodium bicarbonate solution and saturated brine
  5. filtrationThe combined aqueous phases were filtered
  6. washthe filter cake washed with ether
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-adc292611c284408a4afe16ee20e8e20
Source dataset
uspto-grants-2003_07
Patent number
US06599901B1

Reaction notes

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