Cesium carbonate → HCID 24781189, compound

HRID 1024651Notes

Reaction equation

HRID 1024651 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.Br[C:44]1[CH:45]=[N:46][CH:47]=[N:48][CH:49]=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: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]([C:44]3[CH:45]=[N:46][CH:47]=[N:48][CH:49]=3)=[CH:30][CH:29]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 783445-BromopyrimidineHCID 57899408HCID 57899408, compound

Product 1

HCID 24781189HCID 24781189, 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, 0.500 g, 0.829 mmol) in N,N-dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then 5-bromopyrimidine (0.200 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 2 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 5-(4-chloro-phenyl)-1-(3-methanesulfonyl-phenyl)-6-(4-pyrimidin-5-yl-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one. 1H NMR (DMSO-d6, 400 MHz) δ 9.18 (s, 1H), 9.15 (m, 2H), 8.67 (m, 1H), 8.61 (m, 1H), 8.55 (m, 1H), 7.96 (m, 1H), 7.90 (m, 1H), 7.82 (m, 2H), 7.61 (m, 2H), 7.46 (m, 4H), 3.30 (s, 3H); LC-MS calculated for C28H19ClN6O3S (M+H+) 555.1, found 554.9.

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-eab0f52c87f74ac6a3fb5229771347f0
Source dataset
uspto-grants-2014_05
Patent number
US08722691B2

Reaction notes

Loading…