Sodium hydride → HCID 86663028, compound

HRID 2410762Notes

Reaction equation

HRID 2410762 reaction equation
[H-].[Na+].[F:3][C:4]([F:37])([F:36])[C:5]1[CH:6]=[C:7]([C:11]2[CH:12]=[C:13]([C:32]([O:34][CH3:35])=[O:33])[C:14]3[NH:15][C:16]4[CH:17]=[C:18]([O:24][S:25]([C:28]([F:31])([F:30])[F:29])(=[O:27])=[O:26])[CH:19]=[CH:20][C:21]=4[C:22]=3[N:23]=2)[CH:8]=[CH:9][CH:10]=1.Br[CH2:39][C:40]1[CH:45]=[CH:44][C:43]([O:46][CH3:47])=[CH:42][CH:41]=1>CN(C=O)C>[CH3:47][O:46][C:43]1[CH:44]=[CH:45][C:40]([CH2:39][N:15]2[C:16]3[CH:17]=[C:18]([O:24][S:25]([C:28]([F:31])([F:30])[F:29])(=[O:27])=[O:26])[CH:19]=[CH:20][C:21]=3[C:22]3[N:23]=[C:11]([C:7]4[CH:8]=[CH:9][CH:10]=[C:5]([C:4]([F:3])([F:36])[F:37])[CH:6]=4)[CH:12]=[C:13]([C:32]([O:34][CH3:35])=[O:33])[C:14]2=3)=[CH:41][CH:42]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1650214-Methoxybenzyl bromideHCID 86663027HCID 86663027, compound

Product 1

HCID 86663028HCID 86663028, compoundYield 37%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (22 mg, 0.54 mmol, 60% dispersion in oil) was added to an ice-cooled stirred solution of methyl 2-(3-(trifluoromethyl)phenyl)-7-(trifluoromethylsulfonyloxy)-5H-pyrido[3,2-b]indole-4-carboxylate (200 mg, 0.386 mmol) in DMF (4 ml). This was left stirring until gas evolution stopped. 1-(bromomethyl)-4-methoxybenzene (0.072 ml, 0.502 mmol) was added and the reaction was kept in the ice bath for 2 hr. After an additional 1 hr at RT, the reaction was quenched with a saturated aqueous solution of NH4Cl solution and extracted with EtOAc. The organic extracts were washed with water (5×), brine, and dried with sodium sulfate. Removal of the solvent, followed by radial chromatography (step gradient elution with hexane containing 0 to 5% DCM) afforded methyl 5-(4-methoxybenzyl)-2-(3-(trifluoromethyl)phenyl)-7-(trifluoromethylsulfonyloxy)-5H-pyrido[3,2-b]indole-4-carboxylate (91 mg, 0.14 mmol, 37% yield). MS (ESI) m/z 639.1 (M+H). 1H NMR (500 MHz, chloroform-d) δ ppm 8.55 (1H, d, J=8.55 Hz), 8.42 (1H, s), 8.33 (1H, d, J=7.63 Hz), 8.08 (1H, s), 7.59-7.71 (2H, m), 7.40 (1H, d, J=2.14 Hz), 7.29 (1H, dd, J=8.55, 2.14 Hz), 6.88 (2H, d, J=8.85 Hz), 6.76 (2H, d, J=8.85 Hz), 5.71 (2H, s), 3.86 (3H, s), 3.73 (3H, s).

Workup

  1. temperaturecooled
  2. waitThis was left
  3. customthe reaction was quenched with a saturated aqueous solution of NH4Cl solution
  4. extractionextracted with EtOAc
  5. washThe organic extracts were washed with water (5×), brine
  6. dry with materialdried with sodium sulfate
  7. customRemoval of the solvent
  8. washfollowed by radial chromatography (step gradient elution with hexane containing 0 to 5% DCM)

Sources & evidence

ORD record
ord-affb40fe88bb41b6bafd0cb96f914fbe
Source dataset
uspto-grants-2014_08
Patent number
US08815840B2

Reaction notes

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