Potassium Carbonate → N-[[2-chloro-5-[1-(3,4-dihydro-2H-1-benzopyran-6-yl)-1H-pyrazol-3-yl]-phenyl]methyl]acetamide

HRID 1408426Notes

Reaction equation

HRID 1408426 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[CH:11][NH:10][N:9]=2)=[CH:4][C:3]=1[CH2:13][NH:14][C:15](=[O:17])[CH3:16].CN[C@@H]1CCCC[C@H]1NC.C(=O)([O-])[O-].[K+].[K+].I[C:35]1[CH:36]=[CH:37][C:38]2[O:43][CH2:42][CH2:41][CH2:40][C:39]=2[CH:44]=1>O1CCOCC1.[Cu]I>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[CH:11][N:10]([C:35]3[CH:36]=[CH:37][C:38]4[O:43][CH2:42][CH2:41][CH2:40][C:39]=4[CH:44]=3)[N:9]=2)=[CH:4][C:3]=1[CH2:13][NH:14][C:15](=[O:17])[CH3:16]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 109451636-IodochromanHCID 178474518HCID 178474518, compound

Product 1

HCID 67151164N-[[2-chloro-5-[1-(3,4-dihydro-2H-1-benzopyran-6-yl)-1H-pyrazol-3-yl]-phenyl]methyl]acetamide

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

To a solution of N-[[2-chloro-5-(1H-pyrazol-3-yl)phenyl]methyl]acetamide (i.e. the product of Step B of Synthesis Example 4) (0.25 g, 1.0 mmol) in dioxane (2.5 mL) was added trans-N,N′-dimethylcyclohexane-1,2-diamine (0.065 mL, 0.40 mmol), followed by copper(I) iodide (0.076 g, 0.40 mmol), potassium carbonate (0.83 g, 6.0 mmol) and 3,4-dihydro-6-iodo-2H-1-benzopyran (0.20 g, 0.77 mmol; prepared as cited in Step E of Synthesis Example 4). The reaction mixture was heated at 110° C. for 20 h and then cooled to ambient temperature. The solvent was evaporated, and the residue was taken up in chloroform, washed with water and brine, and then dried (Na2SO4) and concentrated. The crude residue was purified by preparative TLC (2.0% methanol in dichloromethane as eluant) to provide the title product, a compound of the present invention, as a solid (0.11 g).

Workup

  1. temperaturecooled to ambient temperature
  2. customThe solvent was evaporated
  3. washwashed with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe crude residue was purified by preparative TLC (2.0% methanol in dichloromethane as eluant)

Sources & evidence

ORD record
ord-e203d69c26064e799f54b99103077631
Source dataset
uspto-grants-2014_12
Patent number
US08921360B2

Reaction notes

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