Sodium Iodide → 9-[4-(tetrahydro-2H-pyran-4-yloxy)phenyl]-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

HRID 1622650Notes

Reaction equation

HRID 1622650 reaction equation
C(=O)([O-])[O-].[K+].[K+].Br[CH:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.[I-].[Na+].[O:16]=[S:17]1(=[O:34])[CH2:22][CH2:21][N:20]2[CH:23]=[CH:24][CH:25]=[C:26]([C:27]3[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=3)[C:19]2=[N:18]1.[OH-].[Na+]>CS(C)=O>[O:11]1[CH2:12][CH2:13][CH:8]([O:33][C:30]2[CH:29]=[CH:28][C:27]([C:26]3[C:19]4=[N:18][S:17](=[O:34])(=[O:16])[CH2:22][CH2:21][N:20]4[CH:23]=[CH:24][CH:25]=3)=[CH:32][CH:31]=2)[CH2:9][CH2:10]1

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 133496544-BromotetrahydropyranHCID 667478174-(2,2-Dioxido-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazin-9-yl)phenol

Product 1

HCID 667484569-[4-(tetrahydro-2H-pyran-4-yloxy)phenyl]-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxideYield 17%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of potassium carbonate (750 mg), 4-bromotetrahydro-2H-pyran (896 mg), sodium iodide (814 mg) and 4-(2,2-dioxido-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazin-9-yl)phenol (300 mg) in DMSO (5 mL) was stirred at 150° C. overnight and 160° C. for 24 hr. The mixture was poured into 1N NaOH aq. and extracted with EtOAc. The organic layer was separated, washed with 1N NaOH aq. and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc) to give a white solid (66.6 mg). The solid was purified by preparative HPLC (C18, eluted with H2O in acetonitrile containing 0.1% TFA). The desired fraction was neutralized with sat. NaHCO3 aq. and extracted with EtOAc. The organic layer was separated, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title compound (17.0 mg) as a white solid.

Workup

  1. extractionextracted with EtOAc
  2. customThe organic layer was separated
  3. washwashed with 1N NaOH aq. and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc)

Sources & evidence

ORD record
ord-2de14d1329024ddd94a8ee3f7feb5a15
Source dataset
uspto-grants-2014_07
Patent number
US08778934B2

Reaction notes

Loading…