Acetonitrile → 3-(2-Chloropyridin-4-yl)-4-(tetrahydro-2H-pyran-4-yloxy)-1-trityl-1H-pyrazolo[4,3-c]pyridine

HRID 1046485Notes

Reaction equation

HRID 1046485 reaction equation
I[C:2]1[C:6]2[C:7]([O:11][CH:12]3[CH2:17][CH2:16][O:15][CH2:14][CH2:13]3)=[N:8][CH:9]=[CH:10][C:5]=2[N:4]([C:18]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[N:3]=1.[Cl:37][C:38]1[CH:43]=[C:42](B(O)O)[CH:41]=[CH:40][N:39]=1.C(#N)C.C([O-])(=O)C.[K+]>O.ClCCl>[Cl:37][C:38]1[CH:43]=[C:42]([C:2]2[C:6]3[C:7]([O:11][CH:12]4[CH2:17][CH2:16][O:15][CH2:14][CH2:13]4)=[N:8][CH:9]=[CH:10][C:5]=3[N:4]([C:18]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:3]=2)[CH:41]=[CH:40][N:39]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 517044Potassium AcetateHCID 51515952-Chloropyridine-4-boronic acidHCID 66826813HCID 66826813, compound

Product 1

HCID 866736963-(2-Chloropyridin-4-yl)-4-(tetrahydro-2H-pyran-4-yloxy)-1-trityl-1H-pyrazolo[4,3-c]pyridineYield 66.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a microwave vial was charged 3-iodo-4-(tetrahydro-2H-pyran-4-yloxy)-1-trityl-1H-pyrazolo[4,3-c]pyridine (1.00 g, 1.70 mmol), 2-chloropyridin-4-ylboronic acid (0.281 g, 1.79 mmol) and bis(diphenylphosphino)ferrocenepalladium chloride (139 mg, 0.170 mmol). Acetonitrile (11 mL, 210 mmol) and 1.0 M of potassium acetate in water (4.1 mL) were then added and the reaction mixture was degassed with nitrogen for 10 minutes and then heated to 100° C. under microwave irradiation for 30 minutes. Upon reaction completion, the reaction mixture was diluted with dichloromethane, filtered through Celite® and concentrated in vacuo. The crude residue was purified by column chromatography eluting with 0-100% EtOAc in heptane to give the title compound (0.648 g, 66%). LC-MS (Method H): m/z=573.4 [M+H]+; 1.56 min. 1H-NMR (400 MHz, CDCl3): δ 8.37 (d, J=5.2, 1H), 8.13 (s, 1H), 7.80 (d, J=5.2, 1H), 7.54 (d, J=6.2, 1H), 7.35-7.27 (m, 9H), 7.22-7.14 (m, 6H), 5.90 (d, J=6.2, 1H), 5.55-5.46 (m, 1H), 4.01-3.92 (m, 2H), 3.69-3.60 (m, 2H), 2.23-2.13 (m, 2H), 1.99-1.87 (m, 2H).

Workup

  1. customthe reaction mixture was degassed with nitrogen for 10 minutes
  2. customUpon reaction completion
  3. filtrationfiltered through Celite®
  4. concentrationconcentrated in vacuo
  5. customThe crude residue was purified by column chromatography
  6. washeluting with 0-100% EtOAc in heptane

Sources & evidence

ORD record
ord-5bf58d7b441a436691dd5435d1c98cd0
Source dataset
uspto-grants-2013_10
Patent number
US08569281B2

Reaction notes

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