Sodium Carbonate → (9S)-9-(3'-chloro-4'-fluorobiphenyl-4-yl)-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxide

HRID 1405910Notes

Reaction equation

HRID 1405910 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][C:7]=1[F:8].FC(F)(F)S(O[C:18]1[CH:23]=[CH:22][C:21]([C@H:24]2[C:29]3=[N:30][S:31](=[O:35])(=[O:34])[CH2:32][CH2:33][N:28]3[CH2:27][CH2:26][CH2:25]2)=[CH:20][CH:19]=1)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+]>CCO.O.CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([C:18]2[CH:19]=[CH:20][C:21]([C@H:24]3[C:29]4=[N:30][S:31](=[O:35])(=[O:34])[CH2:32][CH2:33][N:28]4[CH2:27][CH2:26][CH2:25]3)=[CH:22][CH:23]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27346603-Chloro-4-fluorophenylboronic Acid (contains varying amounts of Anhydride)HCID 866636154-[(9S)-2,2-dioxido-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazin-9-yl]phenyl trifluoromethanesulfonate

Product 1

HCID 66824264(9S)-9-(3'-chloro-4'-fluorobiphenyl-4-yl)-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazine 2,2-dioxideYield 21%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

Tetrakis(triphenylphosphine)palladium(0) (16 mg) was added to a mixture of (3-chloro-4-fluorophenyl)boronic acid (85 mg), 4-[(9S)-2,2-dioxido-3,4,6,7,8,9-hexahydropyrido[2,1-c][1,2,4]thiadiazin-9-yl]phenyl trifluoromethanesulfonate (100 mg) and sodium carbonate (51.4 mg) in EtOH (3 mL), water (1.5 mL) and DMF (dry) (2 mL). The mixture was stirred at 50° C. under nitrogen for 16 hr. 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), dissolved in MeCN/DMSO (2500/300 μM) and purified by preparative HPLC (C18, eluted with water in acetonitrile containing 0.1% TFA). The desired fractions were neutralized with sat. NaHCO3 aq., extracted with EtOAc and washed with brine. The organic layer was separated, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title compound (20 mg) as a white solid.

Workup

  1. additionSilica-gel was added
  2. customthe volatiles were removed in vacuo
  3. customwas purified by column chromatography (NH silica gel, eluted with MeOH in EtOAc)
  4. dissolutiondissolved in MeCN/DMSO (2500/300 μM)
  5. custompurified by preparative HPLC (C18, eluted with water in acetonitrile containing 0.1% TFA)
  6. extractionextracted with EtOAc
  7. washwashed with brine
  8. customThe organic layer was separated
  9. dry with materialdried over anhydrous magnesium sulfate
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d9236572deed4ec7820733e78b674b9e
Source dataset
uspto-grants-2014_12
Patent number
US08916551B2

Reaction notes

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