Cesium carbonate → 4-((3,5-dimethylisoxazol-4-yl)-methoxy)-N-(5-ethylpyrimidin-2-yl)benzenesulfonamide

HRID 594132Notes

Reaction equation

HRID 594132 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][CH3:9])=[CH:4][N:3]=1.[CH3:10][C:11]1[C:15]([CH2:16][O:17][C:18]2[CH:23]=[CH:22][C:21]([S:24]([NH2:27])(=[O:26])=[O:25])=[CH:20][CH:19]=2)=[C:14]([CH3:28])[O:13][N:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[CH3:10][C:11]1[C:15]([CH2:16][O:17][C:18]2[CH:19]=[CH:20][C:21]([S:24]([NH:27][C:2]3[N:7]=[CH:6][C:5]([CH2:8][CH3:9])=[CH:4][N:3]=3)(=[O:26])=[O:25])=[CH:22][CH:23]=2)=[C:14]([CH3:28])[O:13][N:12]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 35727632-Chloro-5-ethylpyrimidineHCID 898762304-((3,5-Dimethylisoxazol-4-yl)methoxy)benzenesulfonamide

Product 1

HCID 898759674-((3,5-dimethylisoxazol-4-yl)-methoxy)-N-(5-ethylpyrimidin-2-yl)benzenesulfonamideYield 27.6%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalyst2×HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)Catalyst2×HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

A suspension of 2-chloro-5-ethylpyrimidine (0.021 mL, 0.177 mmol), 4-{[(3,5-dimethyl-4-isoxazolyl)methyl]oxy}benzenesulfonamide (50 mg, 0.177 mmol), palladium(II) acetate (0.397 mg, 1.770 μmol), Xantphos (2.048 mg, 3.54 μmol) and cesium carbonate (144 mg, 0.443 mmol) was prepared in 1,4-dioxane (2 mL). The reaction vessel was sealed and heated by microwaves to 130° C. for 30 minutes. After cooling the reaction, additional Xantphos (2.048 mg, 3.54 μmol) and palladium(II) acetate (0.397 mg, 1.770 μmol) were added. The reaction was heated by microwaves to 130° C. for a further 30 minutes. The reaction mixture was then diluted with methanol (2 mL) and passed through a silica solid phase extraction (SPE) cartridge to remove particulates. The filtrate was evaporated in vacuo and purified by mass directed autoprep (formic acid modifier) to give the title compound (19 mg). LCMS (2 min, formic) Rt 0.93 min, m/z (ES+) 389 (M+H)

Workup

  1. customThe reaction vessel was sealed
  2. temperatureAfter cooling
  3. additionwere added
  4. temperatureThe reaction was heated by microwaves to 130° C. for a further 30 minutes
  5. extractionpassed through a silica solid phase extraction (SPE) cartridge
  6. customto remove particulates
  7. customThe filtrate was evaporated in vacuo
  8. custompurified by mass

Sources & evidence

ORD record
ord-355abcb2f8bf4de998616e1120ed2f1f
Source dataset
uspto-grants-2016_01
Patent number
US09242972B2

Reaction notes

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