Ethyl Acetate → 3-Chloro-N-[2,6-dimethyl-3-(4-methyl-2-thienyl)thieno[2,3-b]pyridin-4-yl]benzenesulfonamide

HRID 573638Notes

Reaction equation

HRID 573638 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([CH3:22])=[CH:8][C:9]=2[NH:11][S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=2)(=[O:14])=[O:13])[S:4][C:3]=1[CH3:23].CC1(C)C(C)(C)OB([C:32]2[S:33][CH:34]=[C:35]([CH3:37])[CH:36]=2)O1.C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:21][C:17]1[CH:16]=[C:15]([S:12]([NH:11][C:9]2[CH:8]=[C:7]([CH3:22])[N:6]=[C:5]3[S:4][C:3]([CH3:23])=[C:2]([C:32]4[S:33][CH:34]=[C:35]([CH3:37])[CH:36]=4)[C:10]=23)(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 104435924,4,5,5-Tetramethyl-2-(4-methylthiophen-2-yl)-1,3,2-dioxaborolaneHCID 68324076N-(3-bromo-2,6-dimethylthieno[2,3-b]pyridin-4-yl)-3-chlorobenzenesulfonamide

Product 1

HCID 683237463-Chloro-N-[2,6-dimethyl-3-(4-methyl-2-thienyl)thieno[2,3-b]pyridin-4-yl]benzenesulfonamideYield 36.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

Under nitrogen, N-(3-bromo-2,6-dimethylthieno[2,3-b]pyridin-4-yl)-3-chlorobenzenesulfonamide (Example 61) (100 mg, 0.232 mmol) was dissolved in 1,4-dioxane (2 mL) and water (0.7 mL). 4,4,5,5-Tetramethyl-2-(4-methyl-2-thienyl)-1,3,2-dioxaborolane (78 mg, 0.347 mmol), tetrakis(triphenylphosphine)palladium(0) (26.8 mg, 0.023 mmol) and potassium carbonate (96 mg, 0.695 mmol) were added and the mixture heated in a microwave at 120° C. for 15 min. Ethyl acetate (10 mL) was added and the mixture washed with water (2×5 mL). The organic layer was dried over MgSO4, filtered and the solvent removed in vacuo. The residue was purified by normal phase chromatography, eluting with a gradient of 0-30% ethyl acetate in cyclohexane and further triturated with MeOH, to give the title compound (37.7 mg). LCMS (A) m/z: 449 [M+1]+, Rt 1.53 min (acidic).

Workup

  1. washthe mixture washed with water (2×5 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customthe solvent removed in vacuo
  5. customThe residue was purified by normal phase chromatography
  6. washeluting with a gradient of 0-30% ethyl acetate in cyclohexane
  7. customfurther triturated with MeOH

Sources & evidence

ORD record
ord-439a12cba3da4b5b8d5661827ec37cb7
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

Loading…