Potassium Carbonate → N-[6-Methyl-3-[3-(methyloxy)phenyl]-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]methanesulfonamide

HRID 573669Notes

Reaction equation

HRID 573669 reaction equation
Br[C:2]1[S:16][C:5]2=[N:6][C:7]([CH3:15])=[CH:8][C:9]([NH:10][S:11]([CH3:14])(=[O:13])=[O:12])=[C:4]2[C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=1.[NH:25]1[CH:29]=[C:28](B(O)O)[CH:27]=[N:26]1.C(=O)([O-])[O-].[K+].[K+]>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>[CH3:15][C:7]1[N:6]=[C:5]2[S:16][C:2]([C:28]3[CH:29]=[N:25][NH:26][CH:27]=3)=[C:3]([C:17]3[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH3:24])[CH:18]=3)[C:4]2=[C:9]([NH:10][S:11]([CH3:14])(=[O:13])=[O:12])[CH:8]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 177502781H-Pyrazole-4-boronic acid2×HCID 68323754N-{2-Bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}methanesulfonamide

Product 1

HCID 68323745N-[6-Methyl-3-[3-(methyloxy)phenyl]-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]methanesulfonamideYield 34.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
130 °C

Procedure

To a suspension of N-{2-bromo-6-methyl-3-[3-(methyloxy)phenyl]thieno[2,3-b]pyridin-4-yl}methanesulfonamide (Example 97) (109 mg, 0.255 mmol), 1H-pyrazol-4-ylboronic acid (60 mg, 0.536 mmol) and potassium carbonate (118 mg, 0.854 mmol) in 1,4-dioxane (1.5 mL) and water (0.6 mL), was added tetrakis(triphenylphosphine)palladium(0) (31 mg, 0.027 mmol). The reaction mixture was heated at 130° C. in a microwave reactor for 1 h, followed by the addition of another portion of 1H-pyrazol-4-ylboronic acid (41 mg, 0.366 mmol) and tetrakis(triphenylphosphine)palladium(0) (15 mg, 0.013 mmol). The reaction mixture was heated at 130° C. in a microwave reactor for another 1 h and was then directly loaded onto a silica column, eluting with a gradient of 0-75% of ethyl acetate in cyclohexane and then further purified by MDAP (acidic conditions), to give the title compound (36 mg). LCMS (A) m/z: 413 [M−1]−, Rt 0.97 min (acidic).

Workup

  1. temperatureThe reaction mixture was heated at 130° C. in a microwave reactor for another 1 h
  2. washeluting with a gradient of 0-75% of ethyl acetate in cyclohexane
  3. customfurther purified by MDAP (acidic conditions)

Sources & evidence

ORD record
ord-756bb03c31ba4a7e99cd4414d58a29a7
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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