1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → ethyl (3-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)carbamate

HRID 2178366Notes

Reaction equation

HRID 2178366 reaction equation
I[C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([NH:11][C:12](=[O:16])[O:13][CH2:14][CH3:15])[N:8]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]4[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=4)=[C:20]([O:34][CH3:35])[CH:19]=3)[C:5]2=[N:6][CH:7]=1.[CH3:36][N:37]1[CH:41]=[C:40](B2OC(C)(C)C(C)(C)O2)[CH:39]=[N:38]1>CN(C)C=O.C(=O)([O-])[O-].[Na+].[Na+].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-].[Cl-].[Fe+2].[Pd+2]>[CH3:35][O:34][C:20]1[CH:19]=[C:18]([CH:23]=[CH:22][C:21]=1[O:24][CH2:25][C:26]1[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=1)[CH2:17][N:8]1[C:5]2=[N:6][CH:7]=[C:2]([C:40]3[CH:39]=[N:38][N:37]([CH3:36])[CH:41]=3)[CH:3]=[C:4]2[N:10]=[C:9]1[NH:11][C:12](=[O:16])[O:13][CH2:14][CH3:15]

Participants

6

Reactant 2

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 131733013HCID 131733013, compound

Product 1

HCID 131733014ethyl (3-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)carbamateYield 23%

Reagents, catalysts & solvents 3

HCID 178478645Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolventHCID 10340Sodium CarbonateSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of ethyl (6-iodo-3-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)-3H-imidazo[4,5-b]pyridin-2-yl)carbamate (11.80 g, 20.05 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (5.00 g, 24.03 mmol) in N,N-dimethylformamide (100 mL) and 2M aqueous sodium carbonate solution (10 mL) was added (1,1′-bis(diphenylphosphino)ferrocene)palladium(II) dichloride (0.87 g, 1.19 mmol). The resulting mixture was heated to 80° C. under a nitrogen atmosphere. After 4 h, the mixture was allowed to cool to room temperature and was filtered through Celite. The filtrate was diluted with water (150 mL) and extracted with ethyl acetate (3×200 mL). The combined organic phases were washed with water (300 mL) and brine (2×300 mL), dried over sodium sulfate, filtered, and concentrated. Chromatographic purification (silica gel, 5% methanol in dichloromethane elute) afforded 2.50 g (23%) of ethyl (3-(3-methoxy-4-((4-methoxybenzyl)oxy)benzyl)-6-(1-methyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridin-2-yl)carbamate as a gray solid.

Workup

  1. temperatureto cool to room temperature
  2. filtrationwas filtered through Celite
  3. additionThe filtrate was diluted with water (150 mL)
  4. extractionextracted with ethyl acetate (3×200 mL)
  5. washThe combined organic phases were washed with water (300 mL) and brine (2×300 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customChromatographic purification (silica gel, 5% methanol in dichloromethane elute)

Sources & evidence

ORD record
ord-569e9bc1d30743d3937d5dbeaa939ab9
Source dataset
uspto-grants-2015_06
Patent number
US09067914B1

Reaction notes

Loading…