Ethanesulfonylchloride, 2-chloro- → 9-{4-[3-(1,1-Difluoroethyl)phenoxy]phenyl}-7-methyl-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

HRID 1748044Notes

Reaction equation

HRID 1748044 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:32]=[CH:33][CH:34]=1)[O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[C:25]([NH2:31])=[N:26][CH:27]=[C:28]([CH3:30])[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:32]=[CH:33][CH:34]=1)[O:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]2[C:25]3=[N:31][S:6](=[O:8])(=[O:7])[CH2:5][CH2:4][N:26]3[CH:27]=[C:28]([CH3:30])[CH:29]=2)=[CH:22][CH:23]=1)([F:13])[CH3:12]

Participants

5

Reactant 3

HCID 15385Ethanesulfonylchloride, 2-chloro-HCID 24758Sodium hydrideHCID 667487153-(4-(3-(1,1-Difluoroethyl)phenoxy)phenyl)-5-methylpyridin-2-amine

Product 1

HCID 667481929-{4-[3-(1,1-Difluoroethyl)phenoxy]phenyl}-7-methyl-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%, 96 mg) in THF (dry) (10 mL) was added 2-chloroethanesulfonyl chloride (0.101 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)-5-methylpyridin-2-amine (164 mg) in THF (dry) (10 mL) was added at 0° C. and the mixture was stirred at room temperature under nitrogen overnight. The mixture was quenched with water at 0° C. Water, EtOAc and THF were added and the mixture was extracted. 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 to give 9-{4-[3-(1,1-difluoroethyl)phenoxy]phenyl}-7-methyl-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide as a white solid. Platinum(IV) oxide (30 mg) was added to a solution of the prepared 9-{4-[3-(1,1-difluoroethyl)phenoxy]phenyl}-7-methyl-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide in THF (dry) (15 mL) and MeOH (15 mL). The mixture was stirred at room temperature under hydrogen for 3 hr. Activated carbon was added and the insoluble solid was removed by filtration through silica gel/Celite pad (eluted with EtOAc, to remove catalytic poison). Platinum(IV) oxide (30 mg) was added and the mixture was stirred at room temperature under hydrogen overnight. Activated carbon was added and the insoluble solid was removed by filtration through silica gel/Celite pad (eluted with EtOAc) and the filtrate was concentrated in vacuo. The residue was crystallized from THF/IPE to give the title compound (47.6 mg) as colorless crystals.

Workup

  1. stirringthe mixture was stirred at room temperature under nitrogen overnight
  2. customThe mixture was quenched with water at 0° C
  3. additionWater, EtOAc and THF were added
  4. extractionthe mixture was extracted
  5. additionSilica-gel was added to the organic phase
  6. customthe volatiles were removed in vacuo
  7. customwas purified by column chromatography (silica gel, eluted with MeOH in EtOAc)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-21fa90bc0eef40ebb4c5946af4a4a333
Source dataset
uspto-grants-2015_10
Patent number
US09150591B2

Reaction notes

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