Potassium Carbonate → methyl N-[[2-chloro-5-(1-spiro[2H-1-benzopyran-3(4H), 2'-[1,3]dioxolan]-6-yl-1H-pyrazol-3-yl)phenyl]methyl]carbamate

HRID 1408433Notes

Reaction equation

HRID 1408433 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:48][CH2:47][C:42]3([O:46][CH2:45][CH2:44][O:43]3)[CH2:41][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:48][CH2:47][C:42]5([O:43][CH2:44][CH2:45][O:46]5)[CH2:41][C:40]=4[CH:49]=3)[N:9]=2)=[CH:4][C:3]=1[CH2:13][NH:14][C:15](=[O:18])[O:16][CH3:17]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 671512246-Bromospiro[2H-1-benzopyran-3(4H),2'-[1,3]dioxolane]HCID 178502067HCID 178502067, compound

Product 1

HCID 67151202methyl N-[[2-chloro-5-(1-spiro[2H-1-benzopyran-3(4H), 2'-[1,3]dioxolan]-6-yl-1H-pyrazol-3-yl)phenyl]methyl]carbamateYield 18%

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 Example 8, 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 potassium carbonate (1.24 g, 9.05 mmol) were added to the reaction mixture. 6-Bromospiro[2H-1-benzopyran-3(4H),2′-[1,3]dioxolane] (614 mg, 2.26 mmol) was added last and the reaction mixture was heated at 100° C. under a nitrogen atmosphere overnight. After TLC analysis (10% MeOH/CHCl3) shows 80% conversion of starting material, the reaction mixture was concentrated under vacuum. The resultant crude residue was purified on a silica gel column with 1% MeOH/CHCl3 as eluent to give the title compound, a compound of the present invention, (120 mg, 18% yield) as a solid.

Workup

  1. concentrationthe reaction mixture was concentrated under vacuum
  2. customThe resultant crude residue was purified on a silica gel column with 1% MeOH/CHCl3 as eluent

Sources & evidence

ORD record
ord-ce243556125d44748366bd2ac656a2b1
Source dataset
uspto-grants-2014_12
Patent number
US08921360B2

Reaction notes

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