Dimethyl Sulfoxide → HCID 117737069, compound

HRID 1504526Notes

Reaction equation

HRID 1504526 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:11]2[C:20]3[C:15](=[CH:16][C:17]([S:21]([NH:24][C:25]4[CH:29]=[CH:28][O:27][N:26]=4)(=[O:23])=[O:22])=[CH:18][CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:30])[C:5]([O:9][CH3:10])=[N:6][C:7]=1Cl.[CH:31]1([NH2:36])[CH2:35][CH2:34][CH2:33][CH2:32]1.CCN(C(C)C)C(C)C.CS(C)=O>Cl.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:11]2[C:20]3[C:15](=[CH:16][C:17]([S:21]([NH:24][C:25]4[CH:29]=[CH:28][O:27][N:26]=4)(=[O:23])=[O:22])=[CH:18][CH:19]=3)[CH:14]=[CH:13][C:12]2=[O:30])[C:5]([O:9][CH3:10])=[N:6][C:7]=1[NH:36][CH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 2906CyclopentylamineHCID 81531DiisopropylethylamineHCID 117736975HCID 117736975, compound

Product 1

HCID 117737069HCID 117737069, compoundYield 54.3%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
130 °C

Procedure

A microwave vessel was charged 1-(5,6-dichloro-2-methoxypyridin-3-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (50 mg, 0.107 mmol), cyclopentanamine (456 μl, 5.35 mmol), hunig's base (93 μl, 0.535 mmol) and DMSO (1070 μl). The vial was sealed and heated to 130° C. for 2 hrs in a Biotage Initiator microwave reactor. The reaction mixture was brought to ambient temperature and then diluted with 1N HCl and Ethyl Acetate. The layers were separated, and the aq. layer was extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude residue was purified by chromatography on silica gel (100-g SNAP Ultra column, 10-100% EtOAc/Heptanes) to give 1-(5-chloro-6-(cyclopentylamino)-2-methoxypyridin-3-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (30 mg, 0.058 mmol, 54.3% yield) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.66 (br. s, 1 H) 8.72 (d, J=1.71 Hz, 1 H) 8.32-8.35 (m, 1 H) 8.18 (d, J=9.59 Hz, 1 H) 7.86 (dd, J=8.97, 2.23 Hz, 1 H) 7.66 (s, 1 H) 7.00 (d, J=9.02 Hz, 1 H) 6.77 (d, J=9.64 Hz, 1 H) 6.46 (d, J=6.79 Hz, 1 H) 5.57 (br. s., 1 H) 4.30-4.37 (m, 1 H) 3.72 (s, 3 H) 1.99-2.03 (m, 2H) 1.47-1.85 (m, 6 H). m/z (ESI) 516.0 (M+H)+.

Workup

  1. customThe vial was sealed
  2. customwas brought to ambient temperature
  3. customThe layers were separated
  4. extractionthe aq. layer was extracted with EtOAc (2×)
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by chromatography on silica gel (100-g SNAP Ultra column, 10-100% EtOAc/Heptanes)

Sources & evidence

ORD record
ord-11f5a50c89f84993934f4367522babf8
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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