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

HRID 909944Notes

Reaction equation

HRID 909944 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]=[C:45]([CH3:49])[N:46]([CH3:48])[CH: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: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:15]=[CH:16][CH:17]=[C:18]([C:43]3[N:44]=[C:45]([CH3:49])[N:46]([CH3:48])[CH:47]=3)[CH:19]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 72048754-Bromo-1,2-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 59290449N-Cyclohexyl-N-(2,2-dimethoxyethyl)-3-(3-(1,2-dimethyl-1H-imidazol-4-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)] (360 mg), potassium carbonate (203 mg), Pd(Ph3P)4 (42.5 mg) and 4-bromo-1,2-dimethyl-1H-imidazole (193 mg) in MeOH (3 mL) was loaded into a microwave vial, flushed with nitrogen and sealed. The reaction mixture was heated within a Discover microwave at 120° C. for 20 min. After cooling, the mixture was filtered and the filtrate was washed with DCM. Volatiles removed and the residue was purified on silica using 50%-100% EtOAc/iso hexane and then 5% MeOH/DCM to afford the subtitled compound (250 mg). MS [M+H-MeOH]+=426 (MultiMode+) 1H NMR (400 MHz, CDCl3) δ 7.61 and 7.59 (2×s, 1H), 7.53 (d, J=7.7 Hz, 1H), 7.28-7.21 (m, 1H), 7.10-7.03 (m, 2H), 4.62 and 4.37 (2×t, J=5.1 Hz, 1H), 4.26-4.17 and 3.62-3.52 (2×m, 1H), 3.82-3.74 (m, 2H), 3.73-3.64 (m, 2H), 3.60 (s, 3H), 3.41 (s, 3H), 3.38 (s, 3H), 3.37 and 3.29 (2×d, J=4.7 Hz, 2H), 2.94-2.86 (m, 2H), 2.73-2.65 (m, 2H), 2.43 (s, 3H), 1.85-1.73 (m, 2H), 1.73-1.60 (m, 3H), 1.54-1.22 (m, 4H), 1.15-1.01 (m, 1H); a ˜2:1 mixture of rotamers is observed.

Workup

  1. customflushed with nitrogen
  2. customsealed
  3. temperatureAfter cooling
  4. filtrationthe mixture was filtered
  5. washthe filtrate was washed with DCM
  6. customVolatiles removed
  7. customthe residue was purified on silica using 50%-100% EtOAc/iso hexane

Sources & evidence

ORD record
ord-c3da0ff4880c4a9f91a53a69064c7edf
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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