Dichloromethane → N-[3-(1-ethyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide

HRID 45899Notes

Reaction equation

HRID 45899 reaction equation
Br[C:2]1[C:3]([C:9]2[C:10]([F:34])=[C:11]([N:16]([CH2:28][O:29][CH2:30][CH2:31][O:32][CH3:33])[S:17]([C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=3[F:27])(=[O:19])=[O:18])[CH:12]=[CH:13][C:14]=2[F:15])=[N:4][N:5]([CH2:7][CH3:8])[CH:6]=1.[N:35]1[CH:40]=[CH:39][C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37][CH:36]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl>C(COC)OC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH2:7]([N:5]1[CH:6]=[C:2]([C:38]2[CH:39]=[CH:40][N:35]=[CH:36][CH:37]=2)[C:3]([C:9]2[C:10]([F:34])=[C:11]([N:16]([CH2:28][O:29][CH2:30][CH2:31][O:32][CH3:33])[S:17]([C:20]3[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=3[F:27])(=[O:19])=[O:18])[CH:12]=[CH:13][C:14]=2[F:15])=[N:4]1)[CH3:8]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 67183880N-[3-(4-bromo-1-ethyl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide

Product 1

HCID 67184570N-[3-(1-ethyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamideYield 86%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

In a vial suitable for microwave irradiation N-[3-(4-Bromo-1-ethyl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide (288 mg, 0.509 mmol) was dissolved in dimethoxyethane (4.5 mL) and Ar was bubbled through the solution for 5 minutes. Water (0.5 mL) was added, followed by 4-pyridylboronic acid pinacol ester (209 mg, 1.018 mmol, 2 eq), cesium carbonate (497 mg, 1.527 mmol, 3 eq) and Pd(dppf)Cl2.DCM (42 mg, 0.051 mmol, 0.1 eq). The vial was sealed and irradiated in the microwave oven at 100° C. for 30 minutes. The reaction mixture was then filtered over a Celite pad and concentrated under reduced pressure. The residue was taken up with ethyl acetate and washed with saturated aqueous NaHCO3 and brine. The organic phase was dried over Na2SO4 and evaporated to dryness. The crude product was purified by chromatography on silica gel (DCM/MeOH 97:3) to give 247 mg (86% yield) of N-[3-(1-ethyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide as an off-white solid.

Workup

  1. customAr was bubbled through the solution for 5 minutes
  2. additionWater (0.5 mL) was added
  3. customThe vial was sealed
  4. customirradiated in the microwave oven at 100° C. for 30 minutes
  5. filtrationThe reaction mixture was then filtered over a Celite pad
  6. concentrationconcentrated under reduced pressure
  7. washwashed with saturated aqueous NaHCO3 and brine
  8. dry with materialThe organic phase was dried over Na2SO4
  9. customevaporated to dryness
  10. customThe crude product was purified by chromatography on silica gel (DCM/MeOH 97:3)

Sources & evidence

ORD record
ord-17c62e4ac12d42a79397b5c8f401fa29
Source dataset
uspto-grants-2013_09
Patent number
US08541575B2

Reaction notes

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