Potassium Carbonate → HCID 68324084, compound

HRID 573674Notes

Reaction equation

HRID 573674 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[C:23]1[CH:24]=[N:25][NH:26][CH:27]=1.[CH3:28][N:29]([C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1)[CH3:30].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: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]([C:23]4[CH:24]=[N:25][NH:26][CH:27]=4)=[C:2]([C:35]4[CH:34]=[CH:33][CH:32]=[C:31]([N:29]([CH3:30])[CH3:28])[CH:36]=4)[C:10]=23)(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 27625273-(Dimethylamino)benzeneboronic acidHCID 68324082N-[3-bromo-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]-3-chlorobenzenesulfonamide

Product 1

HCID 68324084HCID 68324084, compoundYield 7.4%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
110 °C

Procedure

A mixture of N-[3-bromo-6-methyl-2-(1H-pyrazol-4-yl)thieno[2,3-b]pyridin-4-yl]-3-chlorobenzenesulfonamide (Example 100) (100 mg, 0.207 mmol), 3-(N,N-dimethylamino)-phenylboronic acid (68.2 mg, 0.413 mmol) and tetrakis(triphenylphosphine)palladium(0) (11.9 mg, 10.34 μmol) and potassium carbonate (86 mg, 0.620 mmol) in 1,4-dioxane (1 mL), DMF (0.5 mL) and water (0.25 mL) was heated at 110° C. overnight (ca. 22 h). After cooling to RT, the reaction mixture was filtered through celite and the filtrate concentrated and purified by chromatography on silica, eluting with a gradient of 0-100% ethyl acetate in DCM. The material was then passed through an SCX cartridge, eluting with MeOH (ca. 60 mL) and 2M NH3 in MeOH (60 mL), to give the title compound (8 mg). LCMS (A) m/z: 524 [M+1]+, Rt 1.28 min (acidic).

Workup

  1. temperatureAfter cooling to RT
  2. filtrationthe reaction mixture was filtered through celite
  3. concentrationthe filtrate concentrated
  4. custompurified by chromatography on silica
  5. washeluting with a gradient of 0-100% ethyl acetate in DCM
  6. washeluting with MeOH (ca. 60 mL) and 2M NH3 in MeOH (60 mL)

Sources & evidence

ORD record
ord-9334dd8d54b8462d9b2c5d48e2a2632e
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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