Cesium carbonate → 6-(1H-indazol-4-yl)-1-methyl-N-(4-(methylsulfonyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-amine

HRID 241958Notes

Reaction equation

HRID 241958 reaction equation
Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH:10]=[N:11][NH:12]3)[N:5]=[C:4]2[N:17]([CH3:20])[N:18]=[CH:19][C:3]=12.Cl.[CH3:22][S:23]([C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=1)(=[O:25])=[O:24].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OC(=O)C)C.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH:12]1[C:13]2[C:9](=[C:8]([C:6]3[CH:7]=[C:2]([NH:30][C:29]4[CH:28]=[CH:27][C:26]([S:23]([CH3:22])(=[O:25])=[O:24])=[CH:32][CH:31]=4)[C:3]4[CH:19]=[N:18][N:17]([CH3:20])[C:4]=4[N:5]=3)[CH:16]=[CH:15][CH:14]=2)[CH:10]=[N:11]1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 27351804-(Methylsulfonyl)aniline hydrochlorideHCID 580832344-Chloro-6-(1H-indazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 462203326-(1H-indazol-4-yl)-1-methyl-N-(4-(methylsulfonyl)phenyl)-1H-pyrazolo[3,4-b]pyridin-4-amineYield 17.1%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-chloro-6-(1H-indazol-4-yl)-1-methyl-1H-pyrazolo[3,4-b]pyridine 7 (0.04 g, 0.14 mmol) in dioxane was treated with 4-methylsulphonylaniline hydrochloride (0.058 g, 0.28 mmol) in the presence of (tris(dibenzylidene acetone)dipalladium(0), Pd2(dba)3 (0.13 g, 0.014 mmol), XANPHOS (0.016 g, 0.028 mmol) and cesium carbonate (0.18 g, 0.56 mmol) and the reaction mixture were heated overnight at 100° C. The reaction mixture was diluted with ethylacetate and water. The aqueous portions were extracted with ethyl acetate and the organic portions pooled and dried over anhydrous sodium sulfate. The solvent were removed and the crude material purified (Biotage) to obtain 10 mg of 104. 1H NMR (400 MHz, MeOD) δ 8.69 (s, 1H), 8.12 (s, 1H), 7.97 (d, J=8.7, 2H), 7.78-7.55 (m, 4H), 7.59-7.44 (m, 2H), 4.17 (s, 3H), 3.35 (s, 1H), 3.14 (s, 3H). MS (ESI) m/z 419.2 (M+1)+

Workup

  1. extractionThe aqueous portions were extracted with ethyl acetate
  2. dry with materialdried over anhydrous sodium sulfate
  3. customThe solvent were removed
  4. customthe crude material purified (Biotage)

Sources & evidence

ORD record
ord-46cafb83327844f28b5a43385329f183
Source dataset
uspto-grants-2014_02
Patent number
US08653098B2

Reaction notes

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