Pyridine → (9S)-9-[4-(3-fluoro-5-methylphenoxy)phenyl]-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

HRID 1622846Notes

Reaction equation

HRID 1622846 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[C:6]([CH3:8])[CH:7]=1.[O:12]=[S:13]1(=[O:30])[CH2:18][CH2:17][N:16]2[CH2:19][CH2:20][CH2:21][C@@H:22]([C:23]3[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=3)[C:15]2=[N:14]1.N1C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC#N.C(O[Cu]OC(=O)C)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[C:6]([CH3:8])[CH:7]=1)[O:29][C:26]1[CH:25]=[CH:24][C:23]([C@H:22]2[C:15]3=[N:14][S:13](=[O:30])(=[O:12])[CH2:18][CH2:17][N:16]3[CH2:19][CH2:20][CH2:21]2)=[CH:28][CH:27]=1

Participants

7

Reactant 4

HCID 1049PyridineHCID 10796Cesium carbonateHCID 192612653-Fluoro-5-methylbenzeneboronic 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 66748507(9S)-9-[4-(3-fluoro-5-methylphenoxy)phenyl]-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxideYield 38.5%

Reagents, catalysts & solvents 2

HCID 178476681HCID 178476681, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

A mixture of (3-fluoro-5-methylphenyl)boronic acid (824 mg), 4-[(9S)-2,2-dioxido-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazin-9-yl]phenol (500 mg), pyridine (3.60 mL), cesium carbonate (581 mg), diacetoxycopper (648 mg), and powdered 4A MS (5.0 g) in MeCN (18 mL) was stirred at room temperature overnight. The mixture was added with NH silica gel, concentrated in vacuo, and purified by column chromatography (NH silica gel, eluted with EtOAc in hexane then MeOH in EtOAc) then recrystallized from EtOAc to give the title compound (267 mg) as a white solid.

Workup

  1. additionThe mixture was added with NH silica gel
  2. concentrationconcentrated in vacuo
  3. custompurified by column chromatography (NH silica gel
  4. washeluted with EtOAc in hexane
  5. customMeOH in EtOAc) then recrystallized from EtOAc

Sources & evidence

ORD record
ord-bea6c9df96f049df856bc504307f78a4
Source dataset
uspto-grants-2014_07
Patent number
US08778934B2

Reaction notes

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