Potassium Carbonate → 3-[1-(2,6-Dichloro-3-fluorophenyl)ethyl]-5-(1-methyl-1H-imidazol-4-yl)-1H-pyrrolo[2,3-b]pyridine

HRID 2046931Notes

Reaction equation

HRID 2046931 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[CH:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18](B3OC(C)(C)C(C)(C)O3)[CH:19]=2)[NH:14][CH:13]=1)[CH3:11].I[C:31]1[N:32]=[CH:33][N:34]([CH3:36])[CH:35]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[CH:10]([C:12]1[C:20]2[C:15](=[N:16][CH:17]=[C:18]([C:31]3[N:32]=[CH:33][N:34]([CH3:36])[CH:35]=3)[CH:19]=2)[NH:14][CH:13]=1)[CH3:11]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27734634-Iodo-1-methyl-1H-imidazoleHCID 584314473-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 674006443-[1-(2,6-Dichloro-3-fluorophenyl)ethyl]-5-(1-methyl-1H-imidazol-4-yl)-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred mixture of 3-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-5-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (10.0 mg, 0.0229 mmol), 4-iodo-1-methyl-1H-imidazole (7.17 mg, 0.0344 mmol), potassium carbonate (9.53 mg, 0.0689 mmol) in DME (2.0 mL) and H2O (0.40 mL) was added (1,1′-bis-(diphenylphosphino)ferrocene) palladium dichloride (0.84 mg, 0.0011 mmol) under nitrogen atmosphere. The resulting mixture was refluxed at 100° C. for 90 min. The solvent was then removed under reduced pressure and the resulting residue was purified by a flash chromatography (eluent: 2% MeOH in DCM) to give desired product. 1H NMR (400 MHz, CD3OD): δ=1.88 (d, J=7.1 Hz, 3 H), 3.75 (s, 3 H), 5.30 (q, J=6.8 Hz, 1 H), 7.12-7.18 (m, 1 H), 7.22 (d, J=1.5 Hz, 1 H), 7.33 (d, J=1.3 Hz, 1 H), 7.39 (br. s., 1 H), 7.62 (s, 1 H), 7.67 (d, J=2.0 Hz, 1 H), 8.48 (d, J=2.0 Hz, 1H). MS (ES+): m/z 389.05 [MH+]. HPLC: tR=2.54 min (ZQ3, polar—5 min).

Workup

  1. customThe solvent was then removed under reduced pressure
  2. customthe resulting residue was purified by a flash chromatography (eluent: 2% MeOH in DCM)

Sources & evidence

ORD record
ord-a7267c9b1ae74dad9331ba6180b49125
Source dataset
uspto-grants-2013_11
Patent number
US08592448B2

Reaction notes

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