Potassium Carbonate → methyl 6-[3-[4-chloro-3-[[(methoxycarbonyl)amino]-methyl]phenyl]-1H-pyrazol-1-yl]-2H-1-benzopyran-3-carboxylate

HRID 1408430Notes

Reaction equation

HRID 1408430 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:18])[O:16][CH3:17].CN[C@@H]1CCCC[C@H]1NC.C([O-])([O-])=O.[K+].[K+].Br[C:36]1[CH:37]=[CH:38][C:39]2[O:44][CH2:43][C:42]([C:45]([O:47][CH3:48])=[O:46])=[CH:41][C:40]=2[CH:49]=1>O1CCOCC1.[Cu]I.CO.C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:12]=[CH:11][N:10]([C:36]3[CH:37]=[CH:38][C:39]4[O:44][CH2:43][C:42]([C:45]([O:47][CH3:48])=[O:46])=[CH:41][C:40]=4[CH:49]=3)[N:9]=2)=[CH:4][C:3]=1[CH2:13][NH:14][C:15]([O:16][CH3:17])=[O:18]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 15272849Methyl 6-bromo-2H-1-benzopyran-3-carboxylateHCID 178502067HCID 178502067, compound2×

Product 1

HCID 67151153methyl 6-[3-[4-chloro-3-[[(methoxycarbonyl)amino]-methyl]phenyl]-1H-pyrazol-1-yl]-2H-1-benzopyran-3-carboxylateYield 16%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolventHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl N-[[2-chloro-5-(1H-pyrazol-3-yl)phenyl]-methyl]carbamate (i.e. the product of Step B) (400 mg, 1.50 mmol) in dioxane (16 mL) was added trans-N,N′-dimethylcyclohexane-1,2-diamine (0.30 mmol, 43 mg) under a nitrogen atmosphere. Copper (I) iodide (57 mg, 0.30 mmol) and K2CO3 (1.24 g, 9.05 mmol) were added to the reaction mixture. Methyl 6-bromo-2H-1-benzopyran-3-carboxylate (607 mg, 2.26 mmol) was added to the reaction mixture last. The reaction mixture was heated at 100° C. under a nitrogen atmosphere overnight. After TLC analysis (10% MeOH/CHCl3) showed 80% conversion of the starting material, the reaction mixture was cooled and concentrated under vacuum. The crude residue was purified on a silica gel column with 1% MeOH/CHCl3 as eluent to give compound number 23, a compound of the present invention, (110 mg, 16% yield) as solid.

Workup

  1. temperaturethe reaction mixture was cooled
  2. concentrationconcentrated under vacuum
  3. customThe crude residue was purified on a silica gel column with 1% MeOH/CHCl3 as eluent
  4. customto give compound number 23

Sources & evidence

ORD record
ord-42f5735f75894aea86911a143536fa42
Source dataset
uspto-grants-2014_12
Patent number
US08921360B2

Reaction notes

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