Dichloromethane → HCID 66729579, compound

HRID 516639Notes

Reaction equation

HRID 516639 reaction equation
Br[C:2]1[C:3]([C:9]2[C:10]([F:30])=[C:11]([N:15](OC)[S:16]([C:19]3[CH:24]=[C:23]([F:25])[CH:22]=[C:21](C)[C:20]=3[F:27])(=[O:18])=[O:17])[CH:12]=[CH:13][CH:14]=2)=[N:4][N:5]([CH2:7][CH3:8])[CH:6]=1.[N:31]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][CH:32]=1.[C:46](=[O:49])([O-])[O-].[Cs+].[Cs+].[CH2:52](Cl)Cl>COCCOC.O.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:34]2[CH:33]=[CH:32][N:31]=[CH:36][CH:35]=2)[C:3]([C:9]2[C:10]([F:30])=[C:11]([N:15]([CH2:52][O:49][CH3:46])[S:16]([C:19]3[CH:24]=[C:23]([F:25])[CH:22]=[CH:21][C:20]=3[F:27])(=[O:17])=[O:18])[CH:12]=[CH:13][CH:14]=2)=[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 87127779HCID 87127779, compound

Product 1

HCID 66729579HCID 66729579, compoundYield 887.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

In a microwave tube a solution of N-[3-(4-Bromo-1-ethyl-1H-pyrazol-3-yl)-2-fluoro-phenyl]-2,5-difluoro-N-methoxy-methyl-benzenesulfonamide (prepared as described in Example 1) (420 mg, 0.833 mmol) in DME/H2O 9:1 (10 mL) was degassed by bubbling argon for 5 minutes, 4-pyridinyl boronic acid pinacol ester (256 mg, 1.249 mmol, 1.5 eq) was then added, followed by cesium carbonate (543 mg, 1.666 mmol, 2 eq) and Pd(dppf)Cl2.CH2Cl2 (68 mg, 0.083 mmol, 0.1 eq). The mixture was irradiated in the microwave oven at 100° C. for 30 minutes. It was then filtered over a Celite pad, which was washed thoroughly with AcOEt. The filtrate was washed with saturated aqueous NaHCO3 and brine. The organic layer was dried over Na2SO4 and evaporated to dryness. The crude product was purified by chromatography on silica gel (DCM/MeOH 97:3) and 370 mg (88%) of N-[3-(1-Ethyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-2-fluoro-phenyl]-2,5-difluoro-N-methoxymethyl-benzenesulfonamide were obtained as a white solid. HPLC (254 nm): Rt: 6.10 min; 1H NMR (DMSO-d6) Shift: 8.39 (s, 1H), 8.35-8.41 (m, 2H), 7.57-7.65 (m, 1H), 7.45-7.56 (m, 3H), 728-7.39 (m, 2H), 7.04-7.08 (m, 2H), 5.01 (s, 2H), 4.22 (q, J=7.2 Hz, 2H), 3.28 (s, 3H), 1.46 (t, J=7.3 Hz, 3H); HRMS (ESI) calcd for C24H22F3N4O3S [M+H]+ 503.1359. found 503.1342.

Workup

  1. customby bubbling argon for 5 minutes
  2. customThe mixture was irradiated in the microwave oven at 100° C. for 30 minutes
  3. filtrationIt was then filtered over a Celite pad, which
  4. washwas washed thoroughly with AcOEt
  5. washThe filtrate was washed with saturated aqueous NaHCO3 and brine
  6. dry with materialThe organic layer was dried over Na2SO4
  7. customevaporated to dryness
  8. customThe crude product was purified by chromatography on silica gel (DCM/MeOH 97:3)

Sources & evidence

ORD record
ord-89cb3a4a2da64e689c190250aa3979d8
Source dataset
uspto-grants-2015_08
Patent number
US09114137B2

Reaction notes

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