Cesium carbonate → HCID 57899386, compound

HRID 1024599Notes

Reaction equation

HRID 1024599 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[C:12]3[C:15]([S:24]([CH3:27])(=[O:26])=[O:25])=[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: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]=[CH:48][C:47](Br)=[CH:46][N:45]=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]>[NH2:43][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[C:15]([S:24]([CH3:27])(=[O:25])=[O:26])=[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:29][CH:30]=2)=[CH:48][CH:49]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 706222-Amino-5-bromopyridineHCID 57899377HCID 57899377, compound

Product 1

HCID 57899386HCID 57899386, compound

Reagents, catalysts & solvents 1

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

Conditions

Temperature
80 °C

Procedure

A reaction tube charged with 5-(4-chloro-phenyl)-3-methanesulfonyl-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 (200.0 mg, 0.332 mmol), 2-amino-5-bromopyridine (114.8 mg, 0.664 mmol), Cs2CO3 (162.1 mg, 0.498 mmol), and Pd(dppf)2Cl2 (54.2 mg, 0.066 mmol) is purged with nitrogen. Anhydrous DMF (3.3 mL) is added via syringe. The reaction mixture is heated at 80° C. for 2 h, cooled down to room temperature, poured into water (30 mL) and EtOAc (30 mL). The insoluble solid is filtered off and the two layers of the filtrate are separated. The aqueous layer is extracted with EtOAc (2×30 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)-3-methanesulfonyl-1-phenyl-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one as a light yellow solid product; 1H NMR (CDCl3, 400 MHz) δ 8.21 (d, 1H), 8.11 (d, 2H), 7.71 (dd, 1H), 7.54 (t, 2H), 7.44 (t, 1H), 7.41 (m, 4H), 7.36 (d, 2H), 7.16 (d, 2H), 6.67 (d, 1H), 5.22 (br, 2H), 3.55 (s, 3H); HPLC-MS calculated for C29H21ClN6O3S (M+H+) 569.1, found 569.1.

Workup

  1. customis purged with nitrogen
  2. additionAnhydrous DMF (3.3 mL) is added via syringe
  3. temperaturecooled down to room temperature
  4. additionpoured into water (30 mL) and EtOAc (30 mL)
  5. filtrationThe insoluble solid is filtered off
  6. customthe two layers of the filtrate are separated
  7. extractionThe aqueous layer is extracted with EtOAc (2×30 mL)
  8. washThe combined organic phase is washed with brine
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated
  11. custompurified by reverse phase HPLC

Sources & evidence

ORD record
ord-9f0492f249104a0bac10f7495726011d
Source dataset
uspto-grants-2014_05
Patent number
US08722691B2

Reaction notes

Loading…