Sodium Carbonate → Methyl 3-amino-4-[5-cyano-2-(ethoxymethyl)-3-(2-hydroxy-2-methylpropyl)-1H-imidazol-4-yl]benzoate

HRID 63702Notes

Reaction equation

HRID 63702 reaction equation
[CH2:1]([O:3][CH2:4][C:5]1[N:6]([CH2:13][C:14]([OH:17])([CH3:16])[CH3:15])[C:7](I)=[C:8]([C:10]#[N:11])[N:9]=1)[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:37][C:38]1[CH:39]=[C:40]([CH:45]=[CH:46][C:47]=1B1OC(C)(C)C(C)(C)O1)[C:41]([O:43][CH3:44])=[O:42].C([O-])([O-])=O.[Na+].[Na+]>CC([O-])=O.CC([O-])=O.[Pd+2].C(COC)OC>[NH2:37][C:38]1[CH:39]=[C:40]([CH:45]=[CH:46][C:47]=1[C:7]1[N:6]([CH2:13][C:14]([OH:17])([CH3:16])[CH3:15])[CH:5]([CH2:4][O:3][CH2:1][CH3:2])[NH:9][C:8]=1[C:10]#[N:11])[C:41]([O:43][CH3:44])=[O:42]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 44119629Methyl 3-amino-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoateHCID 1184515652-(Ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-5-iodo-1H-imidazole-4-carbonitrile

Product 1

HCID 118451657Methyl 3-amino-4-[5-cyano-2-(ethoxymethyl)-3-(2-hydroxy-2-methylpropyl)-1H-imidazol-4-yl]benzoateYield 71%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

In an inert atmosphere 2-(ethoxymethyl)-1-(2-hydroxy-2-methylpropyl)-5-iodo-1H-imidazole-4-carbonitrile (3.66 g, 10.5 mmol) was combined with dimethoxyethane (43 mL) to give a light brown solution. To this solution were added Pd(OAc)2 (118 mg, 524 μmol), triphenylphosphine (275 mg, 1.05 mmol) and methyl 3-amino-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (4.36 g, 15.7 mmol) with stirring. Finally Na2CO3 (2 M, 15.7 mL, 31.4 mmol) was added. The reaction mixture was heated to 100° C. and stirred for 1 hour. After cooling to room temperature the mixture was partitioned between ethyl acetate (70 mL, 2×50 mL) and water (70 mL). The organic phases were combined, dried over MgSO4, concentrated in vacuo and purified by flash chromatography (silica gel, 0% to 100% ethyl acetate in heptane) to give the title compound (2.79 g, 71%) as light brown foam that was used in the next step without further purification.

Workup

  1. customto give a light brown solution
  2. stirringstirred for 1 hour
  3. temperatureAfter cooling to room temperature the mixture
  4. customwas partitioned between ethyl acetate (70 mL, 2×50 mL) and water (70 mL)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. custompurified by flash chromatography (silica gel, 0% to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-4f899293120a43119a22fa357b2b4dd6
Source dataset
uspto-grants-2016_09
Patent number
US09447097B2

Reaction notes

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