Dichloromethane → HCID 86704203, compound

HRID 1497663Notes

Reaction equation

HRID 1497663 reaction equation
Br[C:2]1[S:6][C:5]([CH:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)=[N:4][C:3]=1[C:13]1[C:14]([F:34])=[C:15]([N:19]([CH2:31][O:32][CH3:33])[S:20]([C:23]2[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=2[F:30])(=[O:22])=[O:21])[CH:16]=[CH:17][CH:18]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(Cl)Cl.CO[CH2:46][CH2:47]OC.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]>[F:30][C:24]1[CH:25]=[CH:26][C:27]([F:29])=[CH:28][C:23]=1[S:20]([N:19]([C:15]1[CH:16]=[CH:17][CH:18]=[C:13]([C:3]2[N:4]=[C:5]([CH:7]3[CH2:12][CH2:11][O:10][CH2:9][CH2:8]3)[S:6][C:2]=2[C:47]2[CH:46]=[CH:31][N:19]=[CH:15][C:14]=2[F:34])[C:14]=1[F:34])[CH2:31][O:32][CH3:33])(=[O:22])=[O:21]

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 10796Cesium carbonateHCID 18180031Water 1,2-dimethoxyethaneHCID 86704204HCID 86704204, compound

Product 1

HCID 86704203HCID 86704203, compound

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×

Procedure

N-{3-[5-bromo-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,5-difluoro-N-(methoxymethyl)benzenesulfonamide (105 mg, 0.182 mmol) was dissolved in a microwave tube in a 9:1 DME/H2O mixture (2.2 mL) and argon was bubbled through the solution for 5 min. Cesium carbonate (148 mg, 0.454 mmol, 2.5 eq) was added, followed by 3-F-4-pyridineboronic acid pinacol ester (82 mg, 0.368 mmol, 2 eq) and Pd(dppf)Cl2.DCM (15 mg, 0.018 mmol, 0.1 eq) and the mixture was irradiated in the microwave oven at 100° c. for 30 min. An addition of Pd(dppf)Cl2.DCM (15 mg, 0.018 mmol, 0.1 eq) was made and the mixture underwent a second microwave cycle. The mixture was filtered through a celite pad and the celite was washed thoroughly with ethyl acetate. The filtrate was washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4 and evaporated to dryness. The crude product was purified by flash chromatograpy on silica gel to give 76 mg of 2,5-difluoro-N-{2-fluoro-3-[5-(3-fluoropyridin-4-yl)-2-(tetrahydro-2H-pyran-4-yl)-1,3-thiazol-4-yl]phenyl}-N-(methoxymethyl)benzenesulfonamide impure of a dimeric by-product. This product was treated with a 9:1 TFA/water mixture (1 mL) and stirred at 60° C. for 1 h. The mixture was evaporated to dryness, taken up with DCM and washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography on silica gel (Hex/acetone 65:35) to give 24 mg of the title compound as an off-white solid.

Workup

  1. customwas bubbled through the solution for 5 min
  2. filtrationThe mixture was filtered through a celite pad
  3. washthe celite was washed thoroughly with ethyl acetate
  4. washThe filtrate was washed with saturated aqueous NaHCO3 and brine
  5. dry with materialdried over Na2SO4
  6. customevaporated to dryness
  7. customThe crude product was purified by flash chromatograpy on silica gel

Sources & evidence

ORD record
ord-9e489817542c420ab2de306df148e1ee
Source dataset
uspto-grants-2015_12
Patent number
US09199979B2

Reaction notes

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