Dimethyl Sulfoxide → HCID 117737054, compound

HRID 1504530Notes

Reaction equation

HRID 1504530 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[NH2:7].CS(C)=O.[F:12][C:13]1[CH:14]=[C:15]([C:23]2[CH:28]=[CH:27][C:26]([N:29]3[C:38]4[C:33](=[CH:34][C:35]([S:39](OC5C(F)=C(F)C(F)=C(F)C=5F)(=[O:41])=[O:40])=[CH:36][CH:37]=4)[CH:32]=[CH:31][C:30]3=[O:54])=[C:25]([O:55][CH3:56])[CH:24]=2)[CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C(OCC)(=O)C.C1COCC1>[F:12][C:13]1[CH:14]=[C:15]([C:23]2[CH:28]=[CH:27][C:26]([N:29]3[C:38]4[C:33](=[CH:34][C:35]([S:39]([NH:7][C:2]5[CH:3]=[N:4][CH:5]=[CH:6][N:1]=5)(=[O:40])=[O:41])=[CH:36][CH:37]=4)[CH:32]=[CH:31][C:30]3=[O:54])=[C:25]([O:55][CH3:56])[CH:24]=2)[CH:16]=[C:17]([C:19]([F:20])([F:21])[F:22])[CH:18]=1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 78747AminopyrazineHCID 2733832Lithium HexamethyldisilazideHCID 117737145HCID 117737145, compound

Product 1

HCID 117737054HCID 117737054, compoundYield 70.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A RBF was charged with pyrazin-2-amine (0.047 g, 0.493 mmol) and DMSO (0.948 ml) to give a solution. Perfluorophenyl 1-(3′-fluoro-3-methoxy-5′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (0.250 g, 0.379 mmol) and THF (2.84 ml) were added, and the mixture remained a solution. The flask was cooled in an ice-bath for 5 min, then lithium bis(trimethylsilyl)amide (1M in THF) (0.872 ml, 0.872 mmol) was added dropwise. The reaction was stirred for 15 minutes. The reaction was diluted with ethyl acetate and washed twice with 1N HCl solution. The organic layers was washed with brine, dried with sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 40 g, gradient elution 0-50% [3:1 EtOAc/EtOH]:Heptane) to afford 1-(3′-fluoro-3-methoxy-5′-(trifluoromethyl)-[1,1′-biphenyl]-4-yl)-2-oxo-N-(pyrazin-2-yl)-1,2-dihydroquinoline-6-sulfonamide (0.153 g, 0.268 mmol, 70.7% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ=11.62 (br. s., 1H), 8.47 (d, J=2.2 Hz, 1H), 8.36 (d, J=1.1 Hz, 1H), 8.29-8.19 (m, 3H), 8.09 (d, J=9.9 Hz, 1H), 8.03 (s, 1H), 7.94 (dd, J=2.2, 9.0 Hz, 1H), 7.75 (d, J=8.6 Hz, 1H), 7.66 (d, J=1.8 Hz, 1H), 7.58 (dd, J=1.9, 8.1 Hz, 1H), 7.44 (d, J=8.1 Hz, 1H), 6.79 (dd, J=9.3, 13.7 Hz, 2H), 3.80 (s, 3H). m/z (ESI) 571.1 (M+H)+.

Workup

  1. customto give a solution
  2. temperatureThe flask was cooled in an ice-bath for 5 min
  3. washwashed twice with 1N HCl solution
  4. washThe organic layers was washed with brine
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe material was purified via column chromatography (RediSep Gold 40 g, gradient elution 0-50% [3:1 EtOAc/EtOH]:Heptane)

Sources & evidence

ORD record
ord-98e9a13199884e44b7b8d98dbc1829f4
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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