Hydrochloric Acid → 1-[1-(4-Fluoro-phenyl)-2-methyl-3,3-dioxo-1,2,3,4-tetrahydro-3lambda*6*-thia-2,4,5-triazaphenanthren-9-yl]-ethanone

HRID 513683Notes

Reaction equation

HRID 513683 reaction equation
Br[C:2]1[C:3]2[C:8]([C:9]3[NH:10][S:11](=[O:25])(=[O:24])[N:12]([CH3:23])[CH:13]([C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)[C:14]=3[CH:15]=1)=[N:7][CH:6]=[CH:5][CH:4]=2.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].[CH2:61]([O:65]C=C)[CH2:62]CC.Cl>C1COCC1.C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:22][C:19]1[CH:18]=[CH:17][C:16]([CH:13]2[C:14]3[CH:15]=[C:2]([C:61](=[O:65])[CH3:62])[C:3]4[C:8](=[N:7][CH:6]=[CH:5][CH:4]=4)[C:9]=3[NH:10][S:11](=[O:24])(=[O:25])[N:12]2[CH3:23])=[CH:21][CH:20]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 8108Butyl vinyl etherHCID 11430Potassium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 681830839-Bromo-1-(4-fluoro-phenyl)-2-methyl-1,4-dihydro-2H-3-thia-2,4,5-triaza-phenanthrene 3,3-dioxide

Product 1

HCID 601635751-[1-(4-Fluoro-phenyl)-2-methyl-3,3-dioxo-1,2,3,4-tetrahydro-3lambda*6*-thia-2,4,5-triazaphenanthren-9-yl]-ethanoneYield 16.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

DMF (2.6 ml) and water (0.6 ml) in a microwave tube were degassed with N2. 9-Bromo-1-(4-fluoro-phenyl)-2-methyl-1,4-dihydro-2H-3-thia-2,4,5-triaza-phenanthrene 3,3-dioxide 399 (100 mg, 0.27 mmol), Pd(OAc)2 (10.6 mg, 0.047 mmol), 1,3-bis(diphenylphosphino)propane (39 mg, 0.09 mmol) and K2CO3 (39 mg, 0.28 mmol) and n-butyl vinylether (154 μl, 1.1 mmol). The mixture was heated in a microwave at 100° C. (200 W, <250 PSi) for 40 min. After cooling, the mixture was diluted with THF (5 ml), acidified with conc. HCl (1 ml) and the mixture was stirred at room temperature for 14 h. The organic phase was diluted with DCM (30 ml), and washed with HCl solution at pH=5-6 (20 ml). The organic phase was dried (Na2SO4) and concentrated in vacuo. The crude residue was purified by column chromatography with DCM/EtOAc (95:5) to give the title compound (17 mg, 15%).

Workup

  1. customDMF (2.6 ml) and water (0.6 ml) in a microwave tube were degassed with N2
  2. temperatureAfter cooling
  3. washwashed with HCl solution at pH=5-6 (20 ml)
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified by column chromatography with DCM/EtOAc (95:5)

Sources & evidence

ORD record
ord-eef66915850945048ea98ae36d53fe73
Source dataset
uspto-grants-2015_08
Patent number
US09102688B2

Reaction notes

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