Potassium Carbonate → N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(1,4-dimethyl-1H-imidazol-2-yl)phenethoxy)propanamide

HRID 909943Notes

Reaction equation

HRID 909943 reaction equation
[CH:1]1([N:7]([CH2:30][CH:31]([O:34][CH3:35])[O:32][CH3:33])[C:8](=[O:29])[CH2:9][CH2:10][O:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16](B3OC(C)(C)C(C)(C)O3)[CH:15]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Br[C:43]1[N:44]([CH3:49])[CH:45]=[C:46]([CH3:48])[N:47]=1>CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]1([N:7]([CH2:30][CH:31]([O:32][CH3:33])[O:34][CH3:35])[C:8](=[O:29])[CH2:9][CH2:10][O:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:43]3[N:44]([CH3:49])[CH:45]=[C:46]([CH3:48])[N:47]=3)[CH:15]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 72048772-Bromo-1,4-dimethyl-1H-imidazoleHCID 59290414N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenethoxy)propanamide

Product 1

HCID 59290359N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(1,4-dimethyl-1H-imidazol-2-yl)phenethoxy)propanamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
120 °C

Procedure

N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenethoxy)propanamide [Example 34, Step i)] (390 mg), potassium carbonate (220 mg), Pd(Ph3P)4 (46 mg) and 2-bromo-1,4-dimethyl-1H-imidazole (279 mg) in MeOH (3 mL) was loaded into a microwave vial, flushed with nitrogen and sealed. The vial was heated within a Discover microwave at 120° C. for 30 min. After cooling, the reaction and the filtrate washed with DCM. Volatiles were removed and the residue purified on silica using 20%-100% EtOAc/iso gradient to afford the subtitled compound (358 mg). MS [M+H]+=458 (MultiMode+) 1H NMR (400 MHz, CDCl3) δ 7.51-7.47 (m, 1H), 7.43-7.40 (m, 1H), 7.37-7.30 (m, 1H), 7.27-7.22 (m, 1H), 6.67 (s, 1H), 4.61 and 4.37 (2×t, J=5.2 Hz, 1H), 4.25-4.16 and 3.61-3.51 (2×m, 1H), 3.81-3.74 (m, 2H), 3.73-3.65 (m, 2H), 3.68 (s, 3H), 3.41 (s, 3H), 3.39 (s, 3H), 3.37 and 3.29 (2×d, J=4.9 Hz, 2H), 2.96-2.89 (m, 2H), 2.73-2.65 (m, 2H), 2.26 (s, 3H), 1.85-1.74 (m, 2H), 1.73-1.05 (m, 8H); a ˜2:1 mixture of rotamers is observed.

Workup

  1. customflushed with nitrogen
  2. customsealed
  3. temperatureAfter cooling
  4. customthe reaction
  5. washthe filtrate washed with DCM
  6. customVolatiles were removed
  7. customthe residue purified on silica using 20%-100% EtOAc/iso gradient

Sources & evidence

ORD record
ord-6e9a21376ead46199d26e404f7e84b09
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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