Sodium hydride → 5-[5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid ((R)-2-dimethylcarbamoylmethyl-3-oxo-isoxazolidin-4-yl)-amide

HRID 38039Notes

Reaction equation

HRID 38039 reaction equation
[O:1]=[C:2]1[C@H:6]([NH:7][C:8]([C:10]2[C:14]([CH3:15])=[C:13](/[CH:16]=[C:17]3\[C:18](=[O:27])[NH:19][C:20]4[C:25]\3=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[NH:12][C:11]=2[CH3:28])=[O:9])[CH2:5][O:4][NH:3]1.[H-].[Na+].Br[CH2:32][C:33]([N:35]([CH3:37])[CH3:36])=[O:34]>>[CH3:36][N:35]([CH3:37])[C:33]([CH2:32][N:3]1[C:2](=[O:1])[C@H:6]([NH:7][C:8]([C:10]2[C:14]([CH3:15])=[C:13](/[CH:16]=[C:17]3\[C:18](=[O:27])[NH:19][C:20]4[C:25]\3=[CH:24][C:23]([F:26])=[CH:22][CH:21]=4)[NH:12][C:11]=2[CH3:28])=[O:9])[CH2:5][O:4]1)=[O:34]

Participants

4

Reactant 3

HCID 24758Sodium hydrideHCID 2255442-Bromo-N,N-dimethylacetamideHCID 584325545-[5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid ((R)-3-oxo-isoxazolidin-4-yl)-amide

Product 1

HCID 592160095-[5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid ((R)-2-dimethylcarbamoylmethyl-3-oxo-isoxazolidin-4-yl)-amideYield 13.6%

Procedure

To the solution of 42b (1.0 eq.) cooled on ice bath was added NaH (4.0 or 1.5 eq.). The resulting mixture was stirred for an hour and was then added 2-bromo-N,N-dimethylacetamide (1.0 eq.), the reaction mixture was stirred at room temperature for several hours. LC/MS detection was applied to determine completion of the reaction. DMF was evaporated under reduced pressure and the residue was precipitated with 5% diethylamine/methanol under sonication. The solid was collected by filtration, washed with methanol twice, and further purified by column chromatography to obtain title compound (30 mg, 13.6% yield) as orange solids: 1H NMR (300 MHz, DMSO-d6): δ=13.73 (s, 1H), 10.93 (s, 1H), 8.05-8.08 (d, 1H), 7.74-7.80 (m, 2H), 6.82-6.97 (m, 2H), 5.06-5.15 (q, 1H), 4.39-4.58 (m, 3H), 4.05-4.11 (q, 1H), 2.97 (s, 3H), 2.84 (s, 3H), 2.44-2.47 (ds, 6H). LC/MS: 468.2 [M−H]+.

Workup

  1. customcompletion of the reaction
  2. customDMF was evaporated under reduced pressure
  3. customthe residue was precipitated with 5% diethylamine/methanol under sonication
  4. filtrationThe solid was collected by filtration
  5. washwashed with methanol twice
  6. customfurther purified by column chromatography

Sources & evidence

ORD record
ord-182ccd988a084e2496fb91837380c862
Source dataset
uspto-grants-2013_09
Patent number
US08524709B2

Reaction notes

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