Cesium carbonate → HCID 57899407, compound

HRID 1024609Notes

Reaction equation

HRID 1024609 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: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.[NH2:43][C:44]1[CH:49]=[N:48][C:47](Br)=[CH:46][N:45]=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]>[NH2:43][C:44]1[N:45]=[CH:46][C:47]([C:31]2[CH:32]=[CH:33][C:28]([C:9]3[N:8]([C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)[C:13](=[O:14])[C:12]4[CH:15]=[N:16][N:17]([C:18]5[CH:23]=[CH:22][CH:21]=[C:20]([S:24]([CH3:27])(=[O:26])=[O:25])[CH:19]=5)[C:11]=4[N:10]=3)=[CH:29][CH:30]=2)=[N:48][CH:49]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 5995392-Amino-5-bromopyrazineHCID 57899408HCID 57899408, compound

Product 1

HCID 57899407HCID 57899407, compound

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 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 (prepared as described in example 51, 0.50 g, 0.83 mmol) in N,N-dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then 2-amino-5-bromopyrazine (0.216 g, 1.24 mmol), cesium carbonate (0.540 g, 1.66 mmol), Pd(dppf)2Cl2 (0.060 g, 0.082 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 24 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 6-[4-(5-amino-pyrazin-2-yl)-phenyl]-5-(4-chloro-phenyl)-1-(3-methanesulfonyl-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one. 1H NMR (CDCl3, 400 MHz) δ 8.93 (s, 1H), 8.60 (m, 1H), 8.42 (s, 1H), 8.37 (s, 1H), 8.12 (s, 1H), 7.93 (d, 1H), 7.82 (d, 2H), 7.73 (m, 1H), 7.47 (d, 2H), 7.36 (d, 2H), 7.15 (d, 2H), 5.05 (br, 2H), 3.13 (s, 3H), 3.01 (s, 3H); LC-MS calculated for C28H20ClN7O3S 570.1 (M+H+), found 570.1.

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-04e87400ba7e4469b2ded492f71cfac2
Source dataset
uspto-grants-2014_05
Patent number
US08722691B2

Reaction notes

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