Water → 6-(2-bromo-5-methoxy-benzylsulfanyl)-N-(4-fluoro-phenyl)-nicotinamide

HRID 404758

Reaction equation

HRID 404758 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:17])[C:10]2[CH:15]=[CH:14][C:13]([SH:16])=[N:12][CH:11]=2)=[CH:4][CH:3]=1.Br[CH2:19][C:20]1[CH:25]=[C:24]([O:26][CH3:27])[CH:23]=[CH:22][C:21]=1[Br:28].[OH-].[Na+].O>C(O)C>[Br:28][C:21]1[CH:22]=[CH:23][C:24]([O:26][CH3:27])=[CH:25][C:20]=1[CH2:19][S:16][C:13]1[CH:14]=[CH:15][C:10]([C:9]([NH:8][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)=[O:17])=[CH:11][N:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 35259512-Bromo-5-methoxybenzyl bromideHCID 178522139HCID 178522139, compound

Product 1

HCID 675406656-(2-bromo-5-methoxy-benzylsulfanyl)-N-(4-fluoro-phenyl)-nicotinamideYield 99%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

As described in Method A, N-(4-fluoro-phenyl)-6-mercapto-nicotinamide IIa (745 mg, 3 mmol, 1 eq.) and 2-bromomethyl-4-methoxyphenyl bromide (0.84 g, 3 mmol, 1 eq.) were suspended in ethanol (36 ml). To the suspension, 1 N sodium hydroxide (5.1 ml, 6 mmol, 2 eq.) was added, and the reaction mixture heated to gentle reflux for 2 hours, then water (200 ml) was added to the reaction mixture while still hot. Upon cooling, a white precipitate formed, and this was filtered, washed with 50% aqueous ethanol, then water and dried in the oven to afford 1.33 g (99% yield, >95% purity by LC-MS) of 6-(2-bromo-5-methoxy-benzylsulfanyl)-N-(4-fluoro-phenyl)-nicotinamide, intermediate VII, as an off-white solid. ESI-MS m/z=448.9 [M+H]+.

Workup

  1. temperaturethe reaction mixture heated
  2. temperatureto gentle reflux for 2 hours
  3. temperatureUpon cooling
  4. customa white precipitate formed
  5. filtrationthis was filtered
  6. washwashed with 50% aqueous ethanol
  7. dry with materialwater and dried in the oven

Sources & evidence

ORD record
ord-55c12c3e4fd74fc19bcffad7899ee564
Source dataset
uspto-grants-2014_06
Patent number
US08748623B2

Linked notes

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