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

HRID 38041Notes

Reaction equation

HRID 38041 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.[Na+].[I-].CCN(C(C)C)C(C)C.[H-].[Na+].[Cl-].Cl[CH2:44][CH2:45][N:46]1[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1>CN(C=O)C>[N:46]1([CH2:45][CH2:44][N:3]2[C:2](=[O:1])[C@H:6]([NH:7][C:8]([C:10]3[C:14]([CH3:15])=[C:13](/[CH:16]=[C:17]4\[C:18](=[O:27])[NH:19][C:20]5[C:25]\4=[CH:24][C:23]([F:26])=[CH:22][CH:21]=5)[NH:12][C:11]=3[CH3:28])=[O:9])[CH2:5][O:4]2)[CH2:51][CH2:50][O:49][CH2:48][CH2:47]1

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 438225684-(2-Chloro-ethyl)-morpholine chlorideHCID 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 592159935-[5-Fluoro-2-oxo-1,2-dihydro-indol-(3Z)-ylidenemethyl]-2,4-dimethyl-1H-pyrrole-3-carboxylic acid [(R)-2-(2-morpholin-4-yl-ethyl)-3-oxo-isoxazolidin-4-yl]-amideYield 23.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 42b (200 mg, 0.52 mmol), NaI (78 mg, 0.52 mmol) and DIEA (134 mg, 1.04 mmol) in DMF (25 mL) was added 60% NaH (125 mg, 3.13 mmol) at 0° C. After stirring at room temperature for 1 h, the mixture was added 4-(2-Chloro-ethyl)-morpholine chloride (194 mg, 1.05 mmol). The obtained mixture was stirred 48 h at room temperature. LC-MS was used to detect completion of the reaction. The mixture was evaporated under reduced pressure and the residue was triturated with 5% diethylamine/methanol (25 mL). The solid was collected by filtration which was purified again by column chromatography (CH2Cl2:MeOH=20:1) to provide the title compound (60 mg, 23%) as orange solid. 1H NMR (300 MHz, DMSO-d6): δ=13.59 (s, 1H), 11.53 (s, 1H), 7.79-8.13 (m, 3H), 7.04-7.12 (m, 2H), 5.00-5.06 (q, 1H), 4.57-4.62 (t, 1H), 3.97-4.10 (m, 3H), 3.44-3.58 (m, 4H), 2.78-2.94 (m, 1H), 2.47-2.50 (ds, 6H). LC/MS: 498.2 [M+H]+.

Workup

  1. stirringThe obtained mixture was stirred 48 h at room temperature
  2. customcompletion of the reaction
  3. customThe mixture was evaporated under reduced pressure
  4. customthe residue was triturated with 5% diethylamine/methanol (25 mL)
  5. filtrationThe solid was collected by filtration which
  6. customwas purified again by column chromatography (CH2Cl2:MeOH=20:1)

Sources & evidence

ORD record
ord-4aee266f4e2b4b1b893f45a18add3a1a
Source dataset
uspto-grants-2013_09
Patent number
US08524709B2

Reaction notes

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