Cesium carbonate → HCID 117737381, compound

HRID 1504522Notes

Reaction equation

HRID 1504522 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.C(=O)([O-])[O-].[Cs+].[Cs+].[OH:37][CH2:38][CH:39]1[CH2:41][CH2:40]1>CC(O)C.CS(C)=O>[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:22])=[O:23])=[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[O:37][CH2:38][CH:39]1[CH2:41][CH2:40]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 75644CyclopropanemethanolHCID 117736975HCID 117736975, compound

Product 1

HCID 117737381HCID 117737381, compoundYield 55.8%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

A 5-mL vial was sequentially charged with 1-(5,6-dichloro-2-methoxypyridin-3-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (300 mg, 0.642 mmol), cesium carbonate (154 μl, 1.926 mmol), dimethyl sulfoxide (2.1 mL), and (hydroxymethyl)cyclopropane (130 μL, 1.605 mmol). The vial was sealed with a PTFE lined cap and heated to 90° C. After 16 h, the brown reaction mixture was allowed to cool to RT, then diluted with IPA (3 mL) and filtered through a pad of celite. The pad was rinsed with IPA (2×5 mL) and the filtrate was concentrated under reduced pressure to furnish a brown oil, which was dissolved in DMSO (2 mL) filtered through a 0.2 micron filter and purified by reverse-phase HPLC (Waters XBridge Prep Shield RP18 10 μm OBD 19×100 mm) gradient, 20 to 75% MeCN in water (containing 0.1% trifluoroacetic acid as an additive), flow rate 40 mL/min to afford 1-(5-chloro-6-(cyclopropylmethoxy)-2-methoxy-3-pyridinyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinolinesulfonamide (180 mg, 0.358 mmol, 55.7% yield) as a tan amorphous solid. 1H NMR (500 MHz, DMSO-d6) δ=11.65 (br. s., 1H) 8.72 (s, 1 H) 8.36 (s, 1 H) 8.21 (d, J=9.67 Hz, 1 H) 8.04 (s, 1 H) 7.85 (dd, J=8.95, 1.75 Hz, 1 H) 7.00 (d, J=9.02 Hz, 1 H) 6.79 (d, J=9.67 Hz, 1 H) 6.45 (d, J=1.10 Hz, 1 H) 4.23-4.40 (m, 2 H) 3.78 (s, 3 H) 1.30-1.43 (m, 1 H) 0.62 (d, J=7.66 Hz, 2 H) 0.41 (br. s., 2 H). m/z (ESI) 503.3 (M+H)+.

Workup

  1. customlined cap
  2. temperatureto cool to RT
  3. filtrationfiltered through a pad of celite
  4. washThe pad was rinsed with IPA (2×5 mL)
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customto furnish a brown oil, which
  7. filtrationfiltered through a 0.2 micron
  8. filtrationfilter
  9. custompurified by reverse-phase HPLC (Waters XBridge Prep Shield RP18 10 μm OBD 19×100 mm) gradient, 20 to 75% MeCN in water (
  10. additioncontaining 0.1% trifluoroacetic acid as an additive), flow rate 40 mL/min

Sources & evidence

ORD record
ord-e33f8d452ac84df4ba9941d8416af342
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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