4-Methylmorpholine → 4-Oxo-N-[3-(trifluoromethyl)-5-(vinylsulfonamido)phenyl]-1,4-dihydroquinoline-3-carboxamide

HRID 1915433Notes

Reaction equation

HRID 1915433 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:12][C:13]([C:15]2[C:24](=[O:25])[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[NH:17][CH:16]=2)=[O:14])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.CN1CCOCC1.Cl[CH2:34][CH2:35][S:36](Cl)(=[O:38])=[O:37].C(Cl)Cl.CCOC(C)=O>O1CCOCC1>[O:25]=[C:24]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[NH:17][CH:16]=[C:15]1[C:13]([NH:12][C:4]1[CH:3]=[C:2]([NH:1][S:36]([CH:35]=[CH2:34])(=[O:38])=[O:37])[CH:7]=[C:6]([C:8]([F:10])([F:11])[F:9])[CH:5]=1)=[O:14]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 15385Ethanesulfonylchloride, 2-chloro-HCID 21226138Dichloromethane ethylacetateHCID 57567389HCID 57567389, compound

Product 1

HCID 596873234-Oxo-N-[3-(trifluoromethyl)-5-(vinylsulfonamido)phenyl]-1,4-dihydroquinoline-3-carboxamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a suspension of N-[3-amino-5-(trifluoromethyl)phenyl]-4-oxo-1H-quinoline-3-carboxamide (429) (500 mg 1.4 mmol) in 1,4-dioxane (4 mL) was added NMM (0.4 mL, 3.6 mmol). β-Chloroethylsulfonyl chloride (0.16 mL, 1.51 mmol) was added under an argon atmosphere. The mixture was stirred at room temperature for 6½ h, after which TLC (CH2Cl2-EtOAc, 8:2) showed a new spot with a very similar Rf to the starting material. Another 0.5 eq. of NMM was added, and the mixture was stirred at room temperature overnight. LCMS analysis of the crude mixture showed >85% conversion to the desired product. The mixture was concentrated, treated with 1M HCl (5 mL), and extracted with EtOAc (3×10 mL) and CH2Cl2 (3×10 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated to yield 4-oxo-N-[3-(trifluoromethyl)-5-(vinylsulfonamido)phenyl]-1,4-dihydroquinoline-3-carboxamide as an orange foam (0.495 g, 79%), which was used in the next step without further purification. 1H-NMR (d6-Acetone, 300 MHz) δ 8.92 (s, 1H), 8.41-8.38 (m, 1H), 7.94 (m, 2H), 7.78 (br s, 2H), 7.53-7.47 (m, 1H), 7.30 (s, 1H), 6.87-6.79 (dd, J=9.9 Hz, 1H), 6.28 (d, J=16.5 Hz, 1H), 6.09 (d, J=9.9 Hz, 1H); ESI-MS 436.4 m/z (MH−)

Workup

  1. stirringthe mixture was stirred at room temperature overnight

Sources & evidence

ORD record
ord-be74981a267b4effa689a2c347ffb98b
Source dataset
uspto-grants-2013_12
Patent number
US08614327B2

Reaction notes

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