Sodium Carbonate → N-(2-chloro-5-(4-(1-piperidinyl)-6-quinolinyl)-3-pyridinyl)-4-fluorobenzenesulfonamid

HRID 1963777Notes

Reaction equation

HRID 1963777 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][CH:23]=[C:22]3Cl)=[CH:4][N:3]=1.Br[C:31]1[CH:32]=[C:33](NS(C2C=CC(F)=CC=2)(=O)=O)[C:34](Cl)=[N:35][CH:36]=1.ClC1C2C(=CC=C(B3OC(C)(C)C(C)(C)O3)C=2)N=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].O1CCOCC1>[Cl:1][C:2]1[C:7]([NH:8][S:9]([C:12]2[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=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][CH:23]=[C:22]3[N:35]2[CH2:36][CH2:31][CH2:32][CH2:33][CH2:34]2)=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 44608916N-(2-chloro-5-(4-chloroquinolin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamideHCID 53363354N-(5-bromo-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamideHCID 533634364-Chloro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline

Product 1

HCID 44609543N-(2-chloro-5-(4-(1-piperidinyl)-6-quinolinyl)-3-pyridinyl)-4-fluorobenzenesulfonamid

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

N-(2-chloro-5-(4-chloroquinolin-6-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide. To a 5 mL CEM microwave tube was added N-(5-bromo-2-chloropyridin-3-yl)-4-fluorobenzenesulfonamide (0.4 g, 1 mmol), 4-chloro-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (0.4 g, 1 mmol), sodium carbonate (2 mL, 3 mmol), Pd fibrecat PPh (Sigma-Aldrich, St. Lois, Mo.) (20% wt, 80 mg) and dioxane (3 mL). The vial was sealed and placed into CEM microwave for 20 min. at 120° C., with 100 Watts of power via Powermax. LC/MS showed a desired product mass as the major peak. The reaction mixture was partitioned between DCM/water. The aqueous layer was extracted with DCM (3×10 mL). The combined organic layers were washed with water, brine, dried over MgSO4 and concentrated. The crude product was purified using SiO2 (120 g) chromatography with hexanes:acetone=80%:20% as the solvent system to afford the product as light yellow solid (270 mg). MS (ESI pos. ion) m/z: calc'd for C20H12Cl2FN3O2S: 447.5; found: 448.3 (M+1). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 6.99 (br. s., 1 H) 7.13-7.24 (m, 2 H) 7.60 (d, J=4.68 Hz, 1 H) 7.88 (dd, J=8.99, 4.90 Hz, 2 H) 7.97 (dd, J=8.77, 2.05 Hz, 1 H) 8.28 (d, J=8.77 Hz, 1 H) 8.33 (d, J=2.19 Hz, 1 H) 8.38 (d, J=1.90 Hz, 1 H) 8.52 (d, J=2.34 Hz, 1 H) 8.87 (d, J=4.68 Hz, 1 H).

Workup

  1. customThe vial was sealed

Sources & evidence

ORD record
ord-0b54240b21934ef884ccf4330934e5e9
Source dataset
uspto-grants-2013_04
Patent number
US08415376B2

Reaction notes

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