Propargyl alcohol → HCID 68380182, compound

HRID 573656Notes

Reaction equation

HRID 573656 reaction equation
Br[C:2]1[S:22][C:5]2=[N:6][C:7]([CH3:21])=[CH:8][C:9]([NH:10][S:11]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[CH:15]=3)(=[O:13])=[O:12])=[C:4]2[C:3]=1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=1.[CH2:31]([OH:34])[C:32]#[CH:33].C(N(CC)CC)C>C1COCC1.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:20][C:16]1[CH:15]=[C:14]([S:11]([NH:10][C:9]2[CH:8]=[C:7]([CH3:21])[N:6]=[C:5]3[S:22][C:2]([C:33]#[C:32][CH2:31][OH:34])=[C:3]([C:23]4[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=4)[C:4]=23)(=[O:13])=[O:12])[CH:19]=[CH:18][CH:17]=1

Participants

7

Reactant 3

HCID 7859Propargyl alcoholHCID 8471TriethylamineHCID 53250396N-{2-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-3-chlorobenzenesulfonamide

Product 1

HCID 68380182HCID 68380182, compoundYield 7.5%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of N-{2-bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}-3-chlorobenzenesulfonamide (Example 33) (195 mg, 0.372 mmol), propargyl alcohol (0.033 mL, 0.558 mmol), copper(I) iodide (7.09 mg, 0.037 mmol), bis(triphenylphosphine)palladium(II) chloride (10.45 mg, 0.015 mmol) and triethylamine (0.156 mL, 1.117 mmol) in THF (1.7 mL) was stirred under an atmosphere of nitrogen at 70° C. for 3 h. The mixture was allowed to cool to RT, with stirring, over the weekend. The mixture was then partitioned between a saturated aqueous solution of NaHCO3 (25 mL) and ethyl acetate (50 mL). The aqueous phase was separated and extracted with additional ethyl acetate (25 mL). The organic extracts were combined, washed with brine (25 mL), dried with anhydrous MgSO4, filtered and evaporated to dryness. The residue was purified on silica, eluting with a gradient of 0-100% cyclohexane in ethyl acetate. Further purification on silica, eluting with 0-50% cyclohexane in ethyl acetate, afforded the title compound (14 mg) LCMS (A) m/z: 499 [M+1]+, Rt 1.24 min (acidic).

Workup

  1. temperatureto cool to RT
  2. stirringwith stirring, over the weekend
  3. customThe mixture was then partitioned between a saturated aqueous solution of NaHCO3 (25 mL) and ethyl acetate (50 mL)
  4. customThe aqueous phase was separated
  5. extractionextracted with additional ethyl acetate (25 mL)
  6. washwashed with brine (25 mL)
  7. dry with materialdried with anhydrous MgSO4
  8. filtrationfiltered
  9. customevaporated to dryness
  10. customThe residue was purified on silica
  11. washeluting with a gradient of 0-100% cyclohexane in ethyl acetate
  12. customFurther purification on silica
  13. washeluting with 0-50% cyclohexane in ethyl acetate

Sources & evidence

ORD record
ord-4f2b9c75fd6743b2bd5c60a38c1d74fc
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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