2'-(Dicyclohexylphosphino)-N2,N2,N6,N6-tetramethyl[1,1'-biphenyl]-2,6-diamine → N-(isoxazol-3-yl)-1-(2-methoxy-5-(tetrahydro-2H-pyran-4-yl)phenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide

HRID 1504512Notes

Reaction equation

HRID 1504512 reaction equation
CN(C1C=CC=C(N(C)C)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1)C.Br[C:33]1[CH:34]=[CH:35][C:36]([O:59][CH3:60])=[C:37]([N:39]2[C:48]3[C:43](=[CH:44][C:45]([S:49]([NH:52][C:53]4[CH:57]=[CH:56][O:55][N:54]=4)(=[O:51])=[O:50])=[CH:46][CH:47]=3)[CH:42]=[CH:41][C:40]2=[O:58])[CH:38]=1.[I-].[O:62]1[CH2:67][CH2:66][CH:65]([Zn+])[CH2:64][CH2:63]1>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:55]1[CH:56]=[CH:57][C:53]([NH:52][S:49]([C:45]2[CH:44]=[C:43]3[C:48](=[CH:47][CH:46]=2)[N:39]([C:37]2[CH:38]=[C:33]([CH:65]4[CH2:66][CH2:67][O:62][CH2:63][CH2:64]4)[CH:34]=[CH:35][C:36]=2[O:59][CH3:60])[C:40](=[O:58])[CH:41]=[CH:42]3)(=[O:51])=[O:50])=[N:54]1

Participants

6

Reactant 3

HCID 441561692'-(Dicyclohexylphosphino)-N2,N2,N6,N6-tetramethyl[1,1'-biphenyl]-2,6-diamineHCID 1177371161-(5-Bromo-2-methoxy phenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamideHCID 178506619HCID 178506619, compound

Product 1

HCID 117736956N-(isoxazol-3-yl)-1-(2-methoxy-5-(tetrahydro-2H-pyran-4-yl)phenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamideYield 38.6%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A vial was charged with palladium(ii) acetate (2.83 mg, 0.013 mmol), CPhos (0.011 g, 0.025 mmol) and 1-(5-bromo-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.100 g, 0.210 mmol). (Tetrahydro-2H-pyran-4-yl)zinc(II) iodide (0.26M in TI-IF) (2.423 ml, 0.630 mmol) was added and the reaction was stirred at 50° C. for 1 h. The reaction was diluted with ethyl acetate and washed (×2) with 1N HCl solution. The organics were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by reverse-phase preparative HPLC using an XBridge Prep C18 column, 10 micron OBD, 19×100 mm, 0.1% TFA in CH3CN/H2O, gradient 25% to 95% over 12 min to provide N-(isoxazol-3-yl)-1-(2-methoxy-5-(tetrahydro-2H-pyran-4-yl)phenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (0.039 g, 0.081 mmol, 38.6% yield) as a white solid. m/z (ESI) 482.2 (M+H)+.

Workup

  1. washwashed (×2) with 1N HCl solution
  2. washThe organics were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by reverse-phase preparative HPLC
  7. customover 12 min

Sources & evidence

ORD record
ord-c6a66a26e03146cb9b224bd4659f4462
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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