Potassium Phosphate, Tribasic → HCID 117737083, compound

HRID 1504503Notes

Reaction equation

HRID 1504503 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl[C:52]1[CH:57]=[CH:56][C:55]([N:58]2[C:67]3[C:62](=[CH:63][C:64]([S:68]([NH:71][C:72]4[CH:76]=[CH:75][O:74][N:73]=4)(=[O:70])=[O:69])=[CH:65][CH:66]=3)[CH:61]=[CH:60][C:59]2=[O:77])=[CH:54][CH:53]=1>O1CCOCC1.O>[O:74]1[CH:75]=[CH:76][C:72]([NH:71][S:68]([C:64]2[CH:63]=[C:62]3[C:67](=[CH:66][CH:65]=2)[N:58]([C:55]2[CH:54]=[CH:53][C:52]([C:5]4[CH:6]=[CH:7][CH:8]=[C:3]([C:2]([F:13])([F:12])[F:1])[CH:4]=4)=[CH:57][CH:56]=2)[C:59](=[O:77])[CH:60]=[CH:61]3)(=[O:70])=[O:69])=[N:73]1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27343883-(Trifluoromethyl)phenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 117737071HCID 117737071, compound

Product 1

HCID 117737083HCID 117737083, compoundYield 19.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A vial was charged with (3-(trifluoromethyl)phenyl)boronic acid (188 mg, 0.991 mmol), S-Phos Precatalyst (25.1 mg, 0.033 mmol), and potassium phosphate (281 mg, 1.322 mmol). The vial was flushed with Ar (g), then a solution of 1-(4-chlorophenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (166 mg, 0.330 mmol) in 1,4-dioxane (1322 μl) was added. Water (330 μl) was then added, and the vial was sealed and heated to 120° C. for 30 min in a Biotage Initiator microwave reactor. The mixture was extracted with EtOAc (3×). The combined organic extracts were concentrated. The residue was taken up in MeOH and filtered through a 0.2 micron filter. The resulting solution was purified by reverse-phase HPLC (25-70% CH3CN/H2O with 0.1% TFA). Fractions containing product were combined and lyophilized to give N-3-isoxazolyl-2-oxo-1-(3′-(trifluoromethyl)-4-biphenylyl)-1,2-dihydro-6-quinolinesulfonamide (32.5 mg, 0.064 mmol, 19.23% yield) as an off-white powder. NMR (400 MHz, DMSO-d6) δ=11.62 (s, 1H), 8.69 (d, J=1.9 Hz, 1H), 8.35 (d, J=2.3 Hz, 1H), 8.21 (d, J=9.5 Hz, 1H), 8.10-8.01 (m, 2H), 7.99-7.94 (m, 2H), 7.83-7.70 (m, 3H), 7.52-7.41 (m, 2H), 6.78 (t, J=9.0 Hz, 2H), 6.40 (d, J=1.9 Hz, 1H). m/z (ESI) 511.9 (M+H)+.

Workup

  1. customThe vial was flushed with Ar (g)
  2. customthe vial was sealed
  3. extractionThe mixture was extracted with EtOAc (3×)
  4. concentrationThe combined organic extracts were concentrated
  5. filtrationfiltered through a 0.2 micron
  6. filtrationfilter
  7. customThe resulting solution was purified by reverse-phase HPLC (25-70% CH3CN/H2O with 0.1% TFA)
  8. additionFractions containing product

Sources & evidence

ORD record
ord-1cfb0ea5df7c42c89173e9aa363104a2
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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