Cesium carbonate → HCID 57899372, compound

HRID 1024608Notes

Reaction equation

HRID 1024608 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:45]=[CH:46][C:47](Br)=[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]>[NH2:43][C:44]1[CH:45]=[CH:46][C:47]([C:31]2[CH:32]=[CH:33][C:28]([C:9]3[N:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=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 6428116-Bromopyridin-3-amineHCID 57899408HCID 57899408, compound

Product 1

HCID 57899372HCID 57899372, 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, 0.60 g, 1.0 mmol) in N,N-dimethylformamide (20 mL) is degassed with argon for 0.5 h. Then 5-amino-2-bromopyridine (0.26 g, 1.5 mmol), cesium carbonate (0.648 g, 1.99 mmol), Pd(dppf)2Cl2 (0.073 g, 0.099 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 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 preparative HPLC to afford 6-[4-(5-amino-pyridin-2-yl)-phenyl]-5-(4-chloro-phenyl)-1-(3-methane-sulfonyl-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one. 1H NMR (CD3OD, 400 MHz) δ 8.94 (m, 1H), 8.60 (m, 1H), 8.41 (s, 1H), 7.95-7.99 (m, 3H), 7.82 (t, 1H), 7.68-7.75 (m, 5H), 7.34-7.39 (m, 4H), 3.19 (s, 3H); LC-MS calculated for C29H21ClN6O3S (M+H+) 569.1, found 569.0.

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-3ba5359c927342289542fd820d135a49
Source dataset
uspto-grants-2014_05
Patent number
US08722691B2

Reaction notes

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