Cesium carbonate → 3-[6-[4-(5-Amino-pyridin-2-yl)-phenyl]-5-(4-chloro-phenyl)-4-oxo-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl]-benzonitrile

HRID 1024617Notes

Reaction equation

HRID 1024617 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:19]=[C:20]([CH:23]=[CH:24][CH:25]=4)[C:21]#[N:22])[C:11]=3[N:10]=[C:9]2[C:26]2[CH:31]=[CH:30][C:29](B3OC(C)(C)C(C)(C)O3)=[CH:28][CH:27]=2)=[CH:4][CH:3]=1.[NH2:41][C:42]1[CH:43]=[CH:44][C:45](Br)=[N:46][CH:47]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.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]>[NH2:41][C:42]1[CH:43]=[CH:44][C:45]([C:29]2[CH:30]=[CH:31][C:26]([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:19]=[C:20]([CH:23]=[CH:24][CH:25]=5)[C:21]#[N:22])[C:11]=4[N:10]=3)=[CH:27][CH:28]=2)=[N:46][CH:47]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 6428116-Bromopyridin-3-amineHCID 578994373-{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}-benzonitrile

Product 1

HCID 578994433-[6-[4-(5-Amino-pyridin-2-yl)-phenyl]-5-(4-chloro-phenyl)-4-oxo-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl]-benzonitrile

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °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}-benzonitrile (prepared as described in example 40, 1.00 g, 1.81 mmol) in N,N-dimethylformamide (25 mL) is added and the resulted mixture is degassed with argon for 0.5 h. Then 5-amino-2-bromopyridine (0.472 g, 2.72 mmol), cesium carbonate (1.18 g, 3.62 mmol), Pd(dppf)2Cl2 (0.147 g, 0.181 mmol) and 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 preparative HPLC to afford 3-[6-[4-(5-amino-pyridin-2-yl)-phenyl]-5-(4-chloro-phenyl)-4-oxo-4,5-dihydro-pyrazolo[3,4-d]pyrimidin-1-yl]-benzonitrile. LC-MS calculated for C29H18ClN7O (M+H+) 516.1, found 516.1.

Workup

  1. customthe resulted mixture is degassed with argon for 0.5 h
  2. temperatureThe reaction mixture is cooled to rt
  3. extractionextracted with ethyl acetate (3×)
  4. washThe combined organic layer is washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-e363aea8b00b4d09a8f8f9757273653c
Source dataset
uspto-grants-2014_05
Patent number
US08722691B2

Reaction notes

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