9-{4-[4-(Trifluoromethyl)phenoxy]phenyl}-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide → 9-{4-[4-(Trifluoromethyl)phenoxy]phenyl}-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

HRID 1622719Notes

Reaction equation

HRID 1622719 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:27]=[CH:26][C:6]([O:7][C:8]2[CH:13]=[CH:12][C:11]([C:14]3[C:19]4=[N:20][S:21](=[O:25])(=[O:24])[CH2:22][CH2:23][N:18]4[CH:17]=[CH:16][CH:15]=3)=[CH:10][CH:9]=2)=[CH:5][CH:4]=1>C1COCC1.CO.[Pt](=O)=O>[F:29][C:2]([F:1])([F:28])[C:3]1[CH:27]=[CH:26][C:6]([O:7][C:8]2[CH:9]=[CH:10][C:11]([CH:14]3[C:19]4=[N:20][S:21](=[O:24])(=[O:25])[CH2:22][CH2:23][N:18]4[CH2:17][CH2:16][CH2:15]3)=[CH:12][CH:13]=2)=[CH:5][CH:4]=1

Participants

5

Reactant 1

HCID 667485279-{4-[4-(Trifluoromethyl)phenoxy]phenyl}-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

Product 1

HCID 667479209-{4-[4-(Trifluoromethyl)phenoxy]phenyl}-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxideYield 58.3%

Reagents, catalysts & solvents 3

HCID 345198Adams' catalystCatalyst2×HCID 887MethanolSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of NaH (60%, 418 mg) in THF (dry) (25 mL) was added 2-chloroethanesulfonyl chloride (0.659 mL) at 0° C. and the mixture was stirred for 5 min at the same temperature. A solution of 3-(4-(4-(trifluoromethyl)phenoxy)phenyl)pyridin-2-amine (690 mg) in THF (dry) (40 mL) was added at 0° C. and the mixture was stirred at room temperature overnight. The mixture was quenched with water at 0° C. Water, EtOAc and THF were added and the extracted organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was washed with IPE/EtOAc, dried in vacuo to give 9-{4-[4-(trifluoromethyl)phenoxy]phenyl}-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide (579.1 mg) as a slightly yellow solid. Platinum(IV) oxide (30 mg) was added to a solution of 9-{4-[4-(trifluoromethyl)phenoxy]phenyl}-3,4-dihydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide (505 mg) in THF (dry) (15 mL) and MeOH (15 mL) and the mixture was stirred at room temperature under hydrogen for 6 hr. Platinum(IV) oxide (30 mg), MeOH (15 mL) and THF (dry) (15 mL) were added and the mixture was stirred at 50° C. under hydrogen overnight. Activated carbon was added and the insoluble solid was removed by filtration through NH-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 (297.2 mg) as colorless crystals.

Workup

  1. stirringthe mixture was stirred at 50° C. under hydrogen overnight
  2. additionActivated carbon was added
  3. customthe insoluble solid was removed by filtration through NH-silica gel/Celite pad (eluted with EtOAc)
  4. concentrationthe filtrate was concentrated in vacuo
  5. customThe residue was crystallized from THF/IPE

Sources & evidence

ORD record
ord-2ac1610836ab45198bc41ff8fd258d0d
Source dataset
uspto-grants-2014_07
Patent number
US08778934B2

Reaction notes

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