Pyridine → (9S)-9-{4-[2-chloro-5-(trifluoromethyl)phenoxy]phenyl}-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

HRID 1748019Notes

Reaction equation

HRID 1748019 reaction equation
N1C=CC=CC=1.[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][C:9]=1B(O)O.[O:21]=[S:22]1(=[O:39])[CH2:27][CH2:26][N:25]2[CH2:28][CH2:29][CH2:30][C@@H:31]([C:32]3[CH:37]=[CH:36][C:35]([OH:38])=[CH:34][CH:33]=3)[C:24]2=[N:23]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC#N.C(O[Cu]OC(=O)C)(=O)C>[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][C:9]=1[O:38][C:35]1[CH:34]=[CH:33][C:32]([C@H:31]2[C:24]3=[N:23][S:22](=[O:39])(=[O:21])[CH2:27][CH2:26][N:25]3[CH2:28][CH2:29][CH2:30]2)=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 10796Cesium carbonateHCID 27826702-Chloro-5-(trifluoromethyl)phenylboronic acidHCID 667484964-[(9S)-2,2-dioxido-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazin-9-yl]phenol

Product 1

HCID 66748026(9S)-9-{4-[2-chloro-5-(trifluoromethyl)phenoxy]phenyl}-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxideYield 0.6%

Reagents, catalysts & solvents 2

HCID 178476681HCID 178476681, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

Diacetoxycopper (907 mg) was added to a mixture of pyridine (0.606 mL), 2-chloro-5-(trifluoromethyl)phenylboronic acid (459 mg), 4-[(9S)-2,2-dioxido-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazin-9-yl]phenol (700 mg) and cesium carbonate (814 mg) in MeCN (25 mL). The mixture was stirred at room temperature under a dry atmosphere with anhydrous calcium chloride tube for 2 days. The insoluble material was removed by filtration, and the filtrate was diluted with water, and extracted with EtOAc. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. Silica-gel was added and the volatiles were removed in vacuo. The mixture supported on silica-gel was purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc) and concentrated in vacuo to give the title compound (5.9 mg) as pale yellow gum.

Workup

  1. customThe insoluble material was removed by filtration
  2. additionthe filtrate was diluted with water
  3. extractionextracted with EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. additionSilica-gel was added
  7. customthe volatiles were removed in vacuo
  8. customwas purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-eeea6583606f4fb3ad6fadeab87fe238
Source dataset
uspto-grants-2015_10
Patent number
US09150591B2

Reaction notes

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