Ethanesulfonylchloride, 2-chloro- → 9-{4-[3-(1,1-Difluoroethyl)phenoxy]phenyl}-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

HRID 2035904Notes

Reaction equation

HRID 2035904 reaction equation
[H-].[Na+].Cl[CH2:4][CH2:5][S:6](Cl)(=[O:8])=[O:7].[F:10][C:11]([C:14]1[CH:15]=[C:16]([CH:31]=[CH:32][CH:33]=1)[O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[C:25]([NH2:30])=[N:26][CH:27]=[CH:28][CH:29]=2)=[CH:20][CH:19]=1)([F:13])[CH3:12]>C1COCC1>[F:10][C:11]([C:14]1[CH:15]=[C:16]([CH:31]=[CH:32][CH:33]=1)[O:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]2[C:25]3=[N:30][S:6](=[O:8])(=[O:7])[CH2:5][CH2:4][N:26]3[CH:27]=[CH:28][CH:29]=2)=[CH:22][CH:23]=1)([F:13])[CH3:12]

Participants

5

Reactant 3

HCID 15385Ethanesulfonylchloride, 2-chloro-HCID 24758Sodium hydrideHCID 667480523-(4-(3-(1,1-Difluoroethyl)phenoxy)phenyl)pyridin-2-amine

Product 1

HCID 667487699-{4-[3-(1,1-Difluoroethyl)phenoxy]phenyl}-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of NaH (60%, 306 mg) in THF (dry) (25 mL) was added 2-chloroethanesulfonyl chloride (0.483 mL) at 0° C. and the mixture was stirred for 10 min at the same temperature. A solution of 3-(4-(3-(1,1-difluoroethyl)phenoxy)phenyl)pyridin-2-amine (499 mg) in THF (dry) (15 mL) was added at 0° C. and the mixture was stirred at room temperature under a dry atmosphere with anhydrous calcium chloride tube overnight. The mixture was quenched with water/THF then water at 0° C. and extracted with EtOAc/THF. Silica-gel was added to the organic phase and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (silica gel, eluted with MeOH in EtOAc) and concentrated in vacuo and washed with IPE to give the title compound (254 mg) as a white solid. A part of product was recrystallized from MeCN/IPE.

Workup

  1. stirringthe mixture was stirred at room temperature under a dry atmosphere with anhydrous calcium chloride tube overnight
  2. customThe mixture was quenched with water/THF
  3. extractionwater at 0° C. and extracted with EtOAc/THF
  4. additionSilica-gel was added to the organic phase
  5. customthe volatiles were removed in vacuo
  6. customwas purified by column chromatography (silica gel, eluted with MeOH in EtOAc)
  7. concentrationconcentrated in vacuo
  8. washwashed with IPE

Sources & evidence

ORD record
ord-06278a77dc28443bbd95fae67a53e6bb
Source dataset
uspto-grants-2013_11
Patent number
US08575154B2

Reaction notes

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