Sodium Carbonate → N-(2-Chloro-5-(6-(2-(trifluoromethyl)pyridin-4-yl)imidazo[1,2-a]pyridin-3-yl)pyridin-3-yl)dimethylaminosulfonamid

HRID 1025392Notes

Reaction equation

HRID 1025392 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:12]=[C:13]([NH:18][S:19]([N:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])[C:14]([Cl:17])=[N:15][CH:16]=3)=[CH:9][N:10]=2)[CH:7]=1.CC1(C)C(C)(C)OB([C:33]2[CH:38]=[CH:37][N:36]=[C:35]([C:39]([F:42])([F:41])[F:40])[CH:34]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O1CCOCC1>[Cl:17][C:14]1[C:13]([NH:18][S:19]([N:22]([CH3:24])[CH3:23])(=[O:21])=[O:20])=[CH:12][C:11]([C:8]2[N:6]3[CH:7]=[C:2]([C:33]4[CH:38]=[CH:37][N:36]=[C:35]([C:39]([F:42])([F:41])[F:40])[CH:34]=4)[CH:3]=[CH:4][C:5]3=[N:10][CH:9]=2)=[CH:16][N:15]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 457857082-(Trifluoromethyl)pyridine-4-boronic acid, pinacol esterHCID 86663319N-(5-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-chloropyridin-3-yl)dimethylaminosulfonamide

Product 1

HCID 46913525N-(2-Chloro-5-(6-(2-(trifluoromethyl)pyridin-4-yl)imidazo[1,2-a]pyridin-3-yl)pyridin-3-yl)dimethylaminosulfonamidYield 27%

Reagents, catalysts & solvents 2

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a 5 mL microwave tube was added N-(5-(6-bromoimidazo[1,2-a]pyridin-3-yl)-2-chloropyridin-3-yl)dimethylaminosulfonamide (0.080 g, 0.186 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)pyridine (0.061 g, 0.223 mmol), 1,1′-bis(diphenylphosphino)ferrocene]dichloride palladium(II) (0.014 g, 0.019 mmol), sodium carbonate (0.232 mL, 0.464 mmol), and dioxane (2 mL). The resulting mixture was sealed and underwent microwave heating at 100° C. for 20 min. The solvent was removed. The residue was partitioned between pH 7-buffer (1M TRIS-HCL) and DCM. The aqueous layer was extracted with DCM (2×10 mL). The combined organic layers were dried over MgSO4 and concentrated. The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep®, 40 g SiO2, DCM:MeOH (2M NH3)=90%:10% Flow=40 mL/min) to afford the desired product as light yellow solid (25.0 mg). MS (ESI pos. ion) m/z: 496.8. Calcd exact mass for C20H16ClF3N6O2S: 496.1. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.92 (s, 6H) 6.93 (br. s., 1H) 7.78 (d, J=4.82 Hz, 1H) 7.91 (d, J=8.77 Hz, 1H) 7.96 (s, 1H) 8.07 (s, 1H) 8.22 (s, 1H) 8.33-8.44 (m, 2H) 8.70 (s, 1H) 8.90 (d, J=5.26 Hz, 1H).

Workup

  1. customThe resulting mixture was sealed
  2. customThe solvent was removed
  3. customThe residue was partitioned between pH 7-buffer (1M TRIS-HCL) and DCM
  4. extractionThe aqueous layer was extracted with DCM (2×10 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated
  7. customThe crude product was purified

Sources & evidence

ORD record
ord-f7403824547844c7bbb4c289862b3150
Source dataset
uspto-grants-2014_05
Patent number
US08729074B2

Reaction notes

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