Potassium Carbonate → Ethyl 4-{[(3-chlorophenyl)sulfonyl]amino}-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate

HRID 573595Notes

Reaction equation

HRID 573595 reaction equation
Br[C:2]1[S:27][C:5]2=[N:6][C:7]([CH3:26])=[C:8]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[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[CH:3]=1.O(C([N:35]1[CH:39]=[C:38](B(O)O)[CH:37]=[N:36]1)=O)C(C)(C)C.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.CN(C=O)C.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:20][C:16]1[CH:15]=[C:14]([S:11]([NH:10][C:9]2[C:8]([C:21]([O:23][CH2:24][CH3:25])=[O:22])=[C:7]([CH3:26])[N:6]=[C:5]3[S:27][C:2]([C:38]4[CH:39]=[N:35][NH:36][CH:37]=4)=[CH:3][C:4]=23)(=[O:13])=[O:12])[CH:19]=[CH:18][CH:17]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 441186751-tert-Butoxycarbonyl-1H-pyrazole-4-boronic acidHCID 68323811Ethyl 2-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridine-5-carboxylate

Product 1

HCID 68380155Ethyl 4-{[(3-chlorophenyl)sulfonyl]amino}-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridine-5-carboxylate

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Alternatively, a mixture of ethyl 2-bromo-4-{[(3-chlorophenyl)sulfonyl]amino}-6-methylthieno[2,3-b]pyridine-5-carboxylate (Description 72) (8 g, 16.33 mmol), 1-tert-butoxylcarbonyl-1H-pyrazole-4-boronic acid, pinacol ester (9.61 g, 32.7 mmol), tetrakis(triphenylphosphine)palladium(0) (0.944 g, 0.817 mmol) and potassium carbonate (6.77 g, 49.0 mmol) in 1,4-dioxane (50 mL), DMF (25 mL) and water (12.5 mL) was heated at 100° C. for ca. 3 h. After cooling to RT, the reaction mixture was filtered through celite and the filtrate was concentrated. The residue was purified by chromatography on silica, eluting with a gradient of 0-100% ethyl acetate in DCM. The resulting material was then passed through an SCX cartridge, eluting with MeOH (ca. 200 mL) followed by 2M NH3 in MeOH (250 mL) and the basic methanolic fractions concentrated, to give the title compound (7.24 g). Some mixed fractions were further purified by MDAP (acidic conditions), to give the title compound (33 mg).

Workup

  1. temperatureAfter cooling to RT
  2. filtrationthe reaction mixture was filtered through celite
  3. concentrationthe filtrate was concentrated
  4. customThe residue was purified by chromatography on silica
  5. washeluting with a gradient of 0-100% ethyl acetate in DCM
  6. washeluting with MeOH (ca. 200 mL)
  7. concentrationthe basic methanolic fractions concentrated

Sources & evidence

ORD record
ord-a4fc0776dda344c19913dd03a69a43dd
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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