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

HRID 1693552Notes

Reaction equation

HRID 1693552 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]=[CH:20][CH:19]=4)[C:11]=3[N:10]=[C:9]2[C:24]2[CH:29]=[CH:28][C:27](B3OC(C)(C)C(C)(C)O3)=[CH:26][CH:25]=2)=[CH:4][CH:3]=1.[NH2:39][C:40]1[CH:45]=[CH:44][C:43](Br)=[CH:42][N:41]=1.C([O-])([O-])=O.[Cs+].[Cs+]>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]>[NH2:39][C:40]1[N:41]=[CH:42][C:43]([C:27]2[CH:28]=[CH:29][C:24]([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]=[CH:20][CH:19]=5)[C:11]=4[N:10]=3)=[CH:25][CH:26]=2)=[CH:44][CH:45]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 706222-Amino-5-bromopyridineHCID 578979725-(4-Chloro-phenyl)-1-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

Product 1

HCID 578979376-[4-(6-Amino-pyridin-3-yl)-phenyl]-5-(4-chloro-phenyl)-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-oneYield 52.2%

Reagents, catalysts & solvents 1

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

Conditions

Temperature
100 °C

Procedure

A reaction tube charged with 5-(4-chloro-phenyl)-1-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 (500.0 mg, 0.953 mmol), 2-amino-5-bromopyridine (247.3 mg, 1.43 mmol), Cs2CO3 (620.8 mg, 1.91 mmol), and Pd(dppf)2Cl2 (38.9 mg, 0.048 mmol) is purged with nitrogen. Anhydrous DMF (9.5 mL) is added via syringe. The reaction mixture is heated at 100° C. for overnight, cooled down to room temperature, then taken in H2O (100 mL) and ethyl acetate (50 mL). The insoluble solid is filtered off and the two layers of the filtrate are separated. The aqueous layer is extracted with ethyl acetate (2×50 mL). The combined organic phase is washed with brine, dried over MgSO4, concentrated, and purified by reverse phase HPLC to provide 6-[4-(6-amino-pyridin-3-yl)-phenyl]-5-(4-chloro-phenyl)-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one (244.2 mg, 52% yield) as a light yellow solid product; 1H NMR (CDCl3, 400 MHz) δ 8.33 (s, 1H), 8.28 (d, 1H), 8.16 (d, 2H), 7.66 (dd, 1H), 7.51 (t, 2H), 7.40 (m, 4H), 7.35 (m, 3H), 7.13 (d, 2H), 6.59 (d, 1H), 4.72 (br, 2H); HPLC-MS calculated for C28H19ClN6O (M+H+) 491.1. Found 491.1.

Workup

  1. customis purged with nitrogen
  2. additionAnhydrous DMF (9.5 mL) is added via syringe
  3. temperaturecooled down to room temperature
  4. filtrationThe insoluble solid is filtered off
  5. customthe two layers of the filtrate are separated
  6. extractionThe aqueous layer is extracted with ethyl acetate (2×50 mL)
  7. washThe combined organic phase is washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-c81b6068819e4d048faa8d796874b539
Source dataset
uspto-grants-2012_04
Patent number
US08158634B2

Reaction notes

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