Dimethylformamide → HCID 16755793, compound

HRID 1024650Notes

Reaction equation

HRID 1024650 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]3C=N[N:17]([C:18]4[CH:19]=[C:20]([S:24]([NH2:27])(=[O:26])=[O:25])[CH:21]=[CH:22][CH:23]=4)[C:11]=3[N:10]=[C:9]2[C:28]2[CH:33]=[CH:32][C:31](B3OC(C)(C)C(C)(C)O3)=[CH:30][CH:29]=2)=[CH:4][CH:3]=1.I[C:44]1[CH:49]=[N:48][CH:47]=[CH:46][N:45]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:56][N:57](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:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]3[N:57]=[CH:56][N:17]([C:18]4[CH:19]=[C:20]([S:24]([NH2:27])(=[O:25])=[O:26])[CH:21]=[CH:22][CH:23]=4)[C:11]=3[N:10]=[C:9]2[C:28]2[CH:33]=[CH:32][C:31]([C:44]3[CH:49]=[N:48][CH:47]=[CH:46][N:45]=3)=[CH:30][CH:29]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 642841IodopyrazineHCID 57899416HCID 57899416, compound

Product 1

HCID 16755793HCID 16755793, compound

Reagents, catalysts & solvents 1

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

Conditions

Temperature
50 °C

Procedure

A solution of 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}-benzene sulfonamide (prepared as described in example 25, 0.500 g, 0.82 mmol) in N,N-dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then 2-iodopyrazine (0.250 g, 1.24 mmol), cesium carbonate (0.530 g, 1.65 mmol), Pd(dppf)2Cl2 (0.06 g, 0.08 mmol) is added and the resulted mixture is degassed with argon for 0.5 h. The reaction mixture is then heated at 50° C. for 12 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 over silica gel (60-120 mesh) to afford 3-[1-(4-chloro-phenyl)-6-oxo-2-(4-pyrazin-2-yl-phenyl)-1,6-dihydro-purin-9-yl]-benzene sulfonamide. 1H NMR (DMSO-d6, 400 MHz) δ 9.24 (m, 1H), 8.69 (m, 1H), 8.63 (m, 1H), 8.30 (m, 1H), 8.02-8.08 (m, 2H), 7.94 (m, 1H), 7.82 (m, 1H), 7.43-7.58 (m, 8H), 7.15 (br, 2H); LC-MS calculated for C27H18ClN7O3S (M+H+) 556.1, found 555.9.

Workup

  1. customthe resulted mixture 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 over silica gel (60-120 mesh)

Sources & evidence

ORD record
ord-b5c288bbe56942b980907d46c5893dde
Source dataset
uspto-grants-2014_05
Patent number
US08722691B2

Reaction notes

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