Trifluoromethanesulfonic acid → N-(isoxazol-3-yl)-2-oxo-1-(2,3',5'-trifluoro-5-hydroxy-[1,1'-biphenyl]-4-yl)-1,2-dihydroquinoline-6-sulfonamide

HRID 1504515Notes

Reaction equation

HRID 1504515 reaction equation
[O:1]1[CH:5]=[CH:4][C:3]([N:6](CC2C=CC(OC)=CC=2)[S:7]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]([C:20]2[C:25]([OH:26])=[CH:24][C:23]([C:27]4[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[CH:28]=4)=[C:22]([F:35])[CH:21]=2)[C:15](=[O:36])[CH:14]=[CH:13]3)(=[O:9])=[O:8])=[N:2]1.FC(F)(F)S(O)(=O)=O>C(Cl)Cl.CS(C)=O>[O:1]1[CH:5]=[CH:4][C:3]([NH:6][S:7]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]([C:20]2[C:25]([OH:26])=[CH:24][C:23]([C:27]4[CH:32]=[C:31]([F:33])[CH:30]=[C:29]([F:34])[CH:28]=4)=[C:22]([F:35])[CH:21]=2)[C:15](=[O:36])[CH:14]=[CH:13]3)(=[O:8])=[O:9])=[N:2]1

Participants

5

Reactant 2

HCID 62406Trifluoromethanesulfonic acidHCID 117737313N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1-(2,3',5'-trifluoro-5-hydroxy-[1,1'-biphenyl]-4-yl)-1,2-dihydroquinoline-6-sulfonamide

Product 1

HCID 117737337N-(isoxazol-3-yl)-2-oxo-1-(2,3',5'-trifluoro-5-hydroxy-[1,1'-biphenyl]-4-yl)-1,2-dihydroquinoline-6-sulfonamideYield 32%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of N-(isoxazol-3-yl)-N-(4-methoxybenzyl)-2-oxo-1-(2,3′,5′-trifluoro-5-hydroxy-[1,1′-biphenyl]-4-yl)-1,2-dihydroquinoline-6-sulfonamide (39.3 mg, 0.062 mmol) in DCM (620 μl) at room temperature was added trifluoromethanesulfonic acid (16.52 μl, 0.186 mmol). The resulting solution was stirred for 1 hour. The solution was then dissolved in 1.5 ml of DMSO and passed through a 0.20 micron filter. An additional 0.5 ml was used to sinse the reaction vial and the solution was passed through the same filter. The resulting DMSO solution was purified by reverse-phase HPLC (Waters XBridge Prep Shield RP18 10 μm OBD 19×100 mm) gradient, 5 to 50% MeCN in water (containing 0.1% ammonium hydroxide as an additive), flow rate 40 mL/min to yield N-(isoxazol-3-yl)-2-oxo-1-(2,3′,5′-trifluoro-5-hydroxy-[1,1′-biphenyl]-4-yl)-1,2-dihydroquinoline-6-sulfonamide (10.2 mgs, 32% yield over two steps).1H NMR (500 MHz, DMSO-d6) □=ppm 6.37 (s, 1 H) 6.78 (d, J=9.17 Hz, 1 H) 6.83 (d, J=8.45 Hz, 1 H) 7.17 (d, J=7.20 Hz, 1 H) 7.30-7.43 (m, 4 H) 7.84 (dd, J=8.95, 2.01 Hz, 1 H) 8.19 (d, J=7.88 Hz, 1 H) 8.31 (s, J=8.04 Hz, 1 H) 8.59 (s, 1 H) 10.06 (br. s., 1 H). m/z (ESI) 513.9 (M+H)+.

Workup

  1. filtrationfilter
  2. customThe resulting DMSO solution was purified by reverse-phase HPLC (Waters XBridge Prep Shield RP18 10 μm OBD 19×100 mm) gradient, 5 to 50% MeCN in water (
  3. additioncontaining 0.1% ammonium hydroxide as an additive), flow rate 40 mL/min

Sources & evidence

ORD record
ord-85e9ceba25a54994afcf6f993704fac5
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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