Acetamide → HCID 11500823, compound

HRID 2224713Notes

Reaction equation

HRID 2224713 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][C:9]2[CH:21]=[CH:20][C:12]([CH2:13][NH:14][CH2:15][CH2:16][CH:17]([CH3:19])[CH3:18])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.[C:22]([NH2:25])(=[O:24])[CH3:23].N[C@@H]1CCCC[C@H]1N.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.[Cu]I>[CH3:18][CH:17]([CH3:19])[CH2:16][CH2:15][NH:14][CH2:13][C:12]1[CH:20]=[CH:21][C:9]([O:8][C:5]2[N:6]=[CH:7][C:2]([NH:25][C:22](=[O:24])[CH3:23])=[CH:3][CH:4]=2)=[CH:10][CH:11]=1

Participants

7

Reactant 4

HCID 178AcetamideHCID 11430Potassium CarbonateHCID 438061,2-Diaminocyclohexane, trans-2×HCID 59717871HCID 59717871, compound

Product 1

HCID 11500823HCID 11500823, compoundYield 5.4%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of [4-(5-Bromo-pyridin-2-yloxy)-benzyl]-(3-methyl-butyl)-amine (0.493 g, 1.411 mmol), acetamide (0.0938 g, 1.588 mmol), and CuI (0.0309 g, 1.622 mmol) in 1,4-dioxane (3.0 ml) is added (+/−)-trans-1,2-diaminocyclohexane (0.020 mL, 1.67 mmol) and K2CO3 (0.400 g, 0.891 mmol). The reaction mixture is then warmed to 100° C. overnight. Additional amounts of CuI (0.0270 mg, 0.142 mmol) and (+/−)-trans-1,2-diaminocyclohexane (0.020 mL, 1.67 mmol) are added. The reaction mixture is placed in a microwave reactor (CEM Discover, 50W) for 60 min. The mixture is filtered through celite, loaded onto silica gel, and eluted with chloroform with a gradient from 10% of methanol to 30% of methanol to give N-(6-{4-[(3-Methyl-butylamino)-methyl]-phenoxy}-pyridin-3-yl)-acetamide (0.025 g, 5%) as a brown oil. 1NMR (400 MHz, CD3OD) δ ppm: 8.30 (d, J=2.7 Hz, 1H), 8.04 (dd, J=2.5, 8.7 Hz, 1H), 7.38 (d, J=8.6 Hz, 2H), 7.07-7.03 (m, 2H), 6.91 (d, J=8.9 Hz, 1H), 3.82 (s, 2H), 2.68 (dd, J=7.7, 8.0 Hz, 2H), 2.18 (s, 3H), 1.70-1.61 (m, 1H), 1.52-1.44 (m, 2H), 0.96 (d, J=6.6 Hz, 6H); MS (ES): [M+H]+ calcd for C19H26N3O2=328.2025, found 328.2000

Workup

  1. customThe reaction mixture is placed in a microwave reactor
  2. filtrationThe mixture is filtered through celite
  3. washeluted with chloroform with a gradient from 10% of methanol to 30% of methanol

Sources & evidence

ORD record
ord-f40e70a3ae3146c88476aaaddf6b2adc
Source dataset
uspto-grants-2008_05
Patent number
US07378448B2

Reaction notes

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