Dimethylformamide → HCID 57899409, compound

HRID 1024643Notes

Reaction equation

HRID 1024643 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16](=[O:17])[C:15]3N=C[N:12]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=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:3]=[CH:4][C:5]([N:8]2[C:16](=[O:17])[C:15]3[CH:56]=[N:57][N:12]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:25])=[O:26])[CH:19]=4)[C:11]=3[N:10]=[C:9]2[C:28]2[CH:29]=[CH:30][C:31]([C:44]3[CH:49]=[N:48][CH:47]=[CH:46][N:45]=3)=[CH:32][CH:33]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 642841IodopyrazineHCID 57899417HCID 57899417, compound

Product 1

HCID 57899409HCID 57899409, compound

Reagents, catalysts & solvents 1

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

Conditions

Temperature
100 °C

Procedure

A solution of 5-(4-chloro-phenyl)-1-(3-methanesulfonyl-phenyl)-6-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-1,5-dihydro-pyrazolo[3,4-d]-pyrimidin-4-one (8, 0.5 g, 0.829 mmol) in N,N-dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then 2-iodopyrazine (0.26 g, 1.2 mmol), cesium carbonate (0.54 g, 1.7 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 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 preparative HPLC to afford 5-(4-chloro-phenyl)-1-(3-methanesulfonyl-phenyl)-6-(4-pyrazin-2-yl-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one (9). 1H NMR (DMSO-d6, 400 MHz) δ 9.25 (s, 1H), 8.71 (m, 1H), 8.68 (m, 1H), 8.63 (m, 1H), 8.61 (m, 1H), 8.55 (m, 1H), 8.09 (m, 2H), 7.95 (m, 1H), 7.88 (m, 1H), 7.62 (m, 2H), 7.45 (m, 4H), 3.30 (s, 3H); LC-MS calculated for C28H19ClN6O3S (M+H+) 555.1, found 555.0.

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 preparative HPLC

Sources & evidence

ORD record
ord-1cc592e97403492b9b79e5ac1e417510
Source dataset
uspto-grants-2014_05
Patent number
US08722691B2

Reaction notes

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