Cesium carbonate → HCID 57899357, compound

HRID 1024645Notes

Reaction equation

HRID 1024645 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]3[CH:15]=[N:16][N:17]([C:18]4[CH:19]=[C:20]([NH:24][S:25]([CH3:28])(=[O:27])=[O:26])[CH:21]=[CH:22][CH:23]=4)[C:11]=3[N:10]=[C:9]2[C:29]2[CH:34]=[CH:33][C:32](B3OC(C)(C)C(C)(C)O3)=[CH:31][CH:30]=2)=[CH:4][CH:3]=1.I[N:45]1[CH:50]=[CH:49][CH:48]=[CH:47][NH:46]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:13](=[O:14])[C:12]3[CH:15]=[N:16][N:17]([C:18]4[CH:19]=[C:20]([NH:24][S:25]([CH3:28])(=[O:26])=[O:27])[CH:21]=[CH:22][CH:23]=4)[C:11]=3[N:10]=[C:9]2[C:29]2[CH:30]=[CH:31][C:32]([C:50]3[N:45]=[N:46][CH:47]=[CH:48][CH:49]=3)=[CH:33][CH:34]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 57899358HCID 57899358, compoundHCID 86634838HCID 86634838, compound

Product 1

HCID 57899357HCID 57899357, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of N-(3-{5-(4-chloro-phenyl)-4-oxo-6-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)phenyl]-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl}-phenyl)-methane sulfonamide (prepared as described in example 35, 0.50 g, 0.81 mmol) in N,N-dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then 2-iodopyridazine (0.25 g, 1.2 mmol), cesium carbonate (0.527 g, 1.61 mmol), Pd(dppf)2Cl2 (0.06 g, 0.08 mmol) are added and the resulting solution is degassed with argon for 0.5 h. The reaction mixture is then heated at 100° C. for 3 h. The reaction mixture is cooled to rt and diluted with water and extracted with ethyl acetate (3×). The combined organic layer is washed with brine, dried over Na2SO4, concentrated, and purified by column chromatography to afford N-{3-[5-(4-chloro-phenyl)-4-oxo-6-(4-pyridazin-3-yl-phenyl)-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl]-phenyl}-methane sulfonamide (0.155 g, 34% yield). 1H NMR (DMSO-dg, 400 MHz) δ 10.15 (br, 1H), 9.22 (m, 1H), 8.52 (s, 1H), 8.22 (d, 1H), 8.06 (m, 3H), 7.83 (m, 1H), 7.81 (m, 1H), 7.62 (m, 2H), 7.52 (m, 1H), 7.42-7.48 (m, 4H), 7.20 (m, 1H), 3.02 (s, 3H); LC-MS calculated for C28H20ClN7O3S (M+H+) 570.1, found 569.9.

Workup

  1. customthe resulting solution is degassed with argon for 0.5 h
  2. temperatureThe reaction mixture is cooled to rt
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate (3×)
  5. washThe combined organic layer is washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. custompurified by column chromatography

Sources & evidence

ORD record
ord-edd3cd4792b0468485a19123e41f24dd
Source dataset
uspto-grants-2014_05
Patent number
US08722691B2

Reaction notes

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