Water → N-(2-Chloro-5-(3-(pyridin-4-yl)quinoxalin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide

HRID 1963794Notes

Reaction equation

HRID 1963794 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5]([C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][CH:28]=2)[N:25]=[CH:24][C:23](Cl)=[N:22]3)=[CH:4][N:3]=1.[N:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1.C([O-])(=O)C.[K+].O>CC(P(C(C)(C)C)C1C=CC=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC=CC=1)(C)C.Cl[Pd]Cl>[Cl:1][C:2]1[C:7]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)(=[O:11])=[O:10])=[CH:6][C:5]([C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][CH:28]=2)[N:25]=[CH:24][C:23]([C:33]2[CH:34]=[CH:35][N:30]=[CH:31][CH:32]=2)=[N:22]3)=[CH:4][N:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 517044Potassium AcetateHCID 2734379(Pyridin-4-yl)boronic acidHCID 53363527N-(2-Chloro-5-(3-chloroquinoxalin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide

Product 1

HCID 53363611N-(2-Chloro-5-(3-(pyridin-4-yl)quinoxalin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamideYield 57%

Reagents, catalysts & solvents 1

HCID 56649816Dichlorobis((di-tert-butyl)phenylphosphine)palladium(II)Catalyst

Conditions

Temperature
90 °C

Procedure

To a 5 mL microwave vial, N-(2-chloro-5-(3-chloroquinoxalin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide (0.106 g, 0.236 mmol), pyridine-4-ylboronic acid (0.0430 g, 0.350 mmol), dichlorobis(di-tert-butylphenylphosphine)palladium(II) (0.0111 g, 0.0178 mmol), potassium acetate (0.0581 g, 0.592 mmol) and water (0.300 ml, 16.7 mmol) were mixed into (4 mL). The mixture was degassed by bubbling nitrogen through for 5 min. The reaction mixture was stirred at 90° C. for 6 h, then at 110° C. for 1.5 h. The reaction mixture was partitioned between Tris-1M HCl pH 7 buffer (20 mL) and EtOAc (20 mL). The aqueous phase was extracted with EtOAc (20 mL). The combined organic phases were washed with saturated aqueous NaCl (40 mL). The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by silica gel column chromatography (eluent: acetone in DCM 0%-50%) to afford a light yellow solid (0.0662 g) as the desired product. MS (ESI pos. ion) m/z calcd for C24H15ClFN5O2S: 491.1; found 491.9 [M+1]. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 7.06-7.23 (m, 3 H) 7.82-7.92 (m, 2 H) 8.01 (dd, J=8.77, 2.05 Hz, 1 H) 8.14 (dd, J=4.53, 1.61 Hz, 2 H) 8.31 (d, J=8.77 Hz, 1 H) 8.40 (t, J=1.83 Hz, 2 H) 8.57 (d, J=2.34 Hz, 1 H) 8.89 (dd, J=4.68, 1.46 Hz, 2 H) 9.42 (s, 1 H).

Workup

  1. customThe mixture was degassed
  2. customby bubbling nitrogen through for 5 min
  3. waitat 110° C. for 1.5 h
  4. customThe reaction mixture was partitioned between Tris-1M HCl pH 7 buffer (20 mL) and EtOAc (20 mL)
  5. extractionThe aqueous phase was extracted with EtOAc (20 mL)
  6. washThe combined organic phases were washed with saturated aqueous NaCl (40 mL)
  7. dry with materialThe organic phase was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude product was purified by silica gel column chromatography (eluent: acetone in DCM 0%-50%)

Sources & evidence

ORD record
ord-51d8d6cc03764e9b8c78c71c07a0c533
Source dataset
uspto-grants-2013_04
Patent number
US08415376B2

Reaction notes

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