Cyclopropylboronic acid → HCID 117737393, compound

HRID 1504523Notes

Reaction equation

HRID 1504523 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(B(O)O)[CH2:33][CH2:32]1>CCOC(C)=O.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[CH:31]1[CH2:33][CH2:32]1

Participants

5

Reactant 2

HCID 2760897Cyclopropylboronic acidHCID 117736975HCID 117736975, compound

Product 1

HCID 117737393HCID 117737393, compoundYield 42.1%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A 20-mL vial was charged with 1-(5,6-dichloro-2-methoxypyridin-3-yl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (200 mg, 0.428 mmol), cyclopropyl boronic acid (66.2 μl, 0.856 mmol), and (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (62.6 mg, 0.086 mmol) then purged with nitrogen. The reaction vessel was then sequentially charged with dioxane (3.2 mL) and an aqueous solution of sodium carbonate (1.1 mL, 1.9 M) via syringe. The vial was sealed with a PTFE line cap and the resultant red reaction mixture was heated to 50° C. After 12 h, the reaction mixture was allowed to cool to ambient temperature and an aqueous solution of 1.0 N HCL (5 mL) was added and the mixture diluted with EtOAc (5 mL). The layers were separated and the aqueous layer was extracted with EtOAc (3×5 mL). The combined organic layers were washed with brine (25 mL), dried over anhydrous sodium sulfate, filtered, and 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-cyclopropyl-2-methoxy-3-pyridinyl)-N-3-isoxazolyl-2-oxo-1,2-dihydro-6-quinolinesulfonamide (85 mg, 0.180 mmol, 42.0% yield) as a white amorphous solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.23 (d, J=1.76 Hz, 1 H) 8.13 (d, J=1.97 Hz, 1 H) 7.74-7.80 (m, 2 H) 7.46 (s, 1 H) 6.82 (d, J=9.64 Hz, 1 H) 6.75 (d, J=9.02 Hz, 1 H) 6.56 (d, J=1.66 Hz, 1 H) 3.76 (s, 3 H) 2.41-2.61 (m, 1 H) 1.14-1.23 (m, 2 H) 1.09 (dd, J=8.09, 3.21 Hz, 2 H). m/z (ESI) 473.0 (M+H)+.

Workup

  1. customthen purged with nitrogen
  2. additionThe reaction vessel was then sequentially charged with dioxane (3.2 mL)
  3. customThe vial was sealed with a PTFE line
  4. customcap
  5. customthe resultant red reaction mixture
  6. temperatureto cool to ambient temperature
  7. additionan aqueous solution of 1.0 N HCL (5 mL) was added
  8. customThe layers were separated
  9. extractionthe aqueous layer was extracted with EtOAc (3×5 mL)
  10. washThe combined organic layers were washed with brine (25 mL)
  11. dry with materialdried over anhydrous sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customto furnish a brown oil, which
  15. filtrationfiltered through a 0.2 micron
  16. filtrationfilter
  17. custompurified by reverse-phase HPLC (Waters XBridge Prep Shield RP18 10 μm OBD 19×100 mm) gradient, 20 to 75% MeCN in water (
  18. additioncontaining 0.1% trifluoroacetic acid as an additive), flow rate 40 mL/min

Sources & evidence

ORD record
ord-f5344c6466604629a4616cba0bd61881
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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