Sodium Iodide → 9-[4-(Cyclopropyloxy)phenyl]-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

HRID 1747915Notes

Reaction equation

HRID 1747915 reaction equation
C(=O)([O-])[O-].[K+].[K+].Br[CH:8]1[CH2:10][CH2:9]1.[O:11]=[S:12]1(=[O:29])[CH2:17][CH2:16][N:15]2[CH:18]=[CH:19][CH:20]=[C:21]([C:22]3[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=3)[C:14]2=[N:13]1.[I-].[Na+].[OH-].[Na+]>CS(C)=O>[CH:8]1([O:28][C:25]2[CH:24]=[CH:23][C:22]([C:21]3[C:14]4=[N:13][S:12](=[O:29])(=[O:11])[CH2:17][CH2:16][N:15]4[CH:18]=[CH:19][CH:20]=3)=[CH:27][CH:26]=2)[CH2:10][CH2:9]1

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 78037Bromocyclopropane2×HCID 667478174-(2,2-Dioxido-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazin-9-yl)phenol

Product 1

HCID 667480839-[4-(Cyclopropyloxy)phenyl]-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxideYield 14.8%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of potassium carbonate (450 mg), bromocyclopropane (394 mg) and 4-(2,2-dioxido-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazin-9-yl)phenol (300 mg) in DMSO (3 mL) was stirred at 130° C. overnight. Then bromocyclopropane (788 mg) and sodium iodide (488 mg) were added and the mixture was stirred at 150° C. for 5 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 to give a brown solid. The solid was purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc) to give 50.9 mg of yellow solid. 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 (26.8 mg) as a white solid.

Workup

  1. stirringthe mixture was stirred at 150° C. for 5 hr
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed with 1N NaOH aq. and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give a brown solid
  8. customThe solid was purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc)

Sources & evidence

ORD record
ord-be11382e6d61438c8ed393c3dd0af744
Source dataset
uspto-grants-2015_10
Patent number
US09150591B2

Reaction notes

Loading…