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

HRID 1747916Notes

Reaction equation

HRID 1747916 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. NaHCO2aq. 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-1c83697419724256af555591c7c5807a
Source dataset
uspto-grants-2015_10
Patent number
US09150591B2

Reaction notes

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