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

HRID 1046486Notes

Reaction equation

HRID 1046486 reaction equation
I[C:2]1[C:6]2[C:7]([O:11][CH3:12])=[N:8][CH:9]=[CH:10][C:5]=2[N:4]([C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[N:3]=1.[Cl:32][C:33]1[CH:38]=[C:37](B(O)O)[CH:36]=[CH:35][N:34]=1.C(#N)C.C([O-])(=O)C.[K+]>O.ClCCl>[Cl:32][C:33]1[CH:38]=[C:37]([C:2]2[C:6]3[C:7]([O:11][CH3:12])=[N:8][CH:9]=[CH:10][C:5]=3[N:4]([C:13]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[N:3]=2)[CH:36]=[CH:35][N:34]=1

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 517044Potassium AcetateHCID 51515952-Chloropyridine-4-boronic acidHCID 668254573-iodo-4-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 866736973-(2-Chloropyridin-4-yl)-4-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridineYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a microwave vial was charged 3-iodo-4-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridine (1.14 g, 2.21 mmol), 2-chloropyridin-4-ylboronic acid (0.366 g, 2.32 mmol) and bis(diphenylphosphino)ferrocenepalladium chloride (181 mg, 0.221 mmol). Acetonitrile (14 mL, 270 mmol) and 1.0 M of potassium acetate in water (5.3 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 40 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 0-2% EtOAc in DCM to give the title compound (0.887 g, 80%). LC-MS (Method H): m/z=503.3 [M+H]+, 1.55 min. 1H-NMR (400 MHz, CDCl3): δ 8.38 (d, J=4.6, 1H), 8.06 (s, 1H), 7.86 (d, J=4.8, 1H), 7.58 (d, J=6.0, 1H), 7.35-7.28 (m, 9H), 7.23-7.14 (m, 6H), 5.91 (d, J=6.2, 1H), 4.11 (s, 3H.

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 0-2% EtOAc in DCM

Sources & evidence

ORD record
ord-7adae0c7dfa3467f8ed1d7a18d2d5199
Source dataset
uspto-grants-2013_10
Patent number
US08569281B2

Reaction notes

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