Methyl iodide → 4-(2,5-Dichloro-phenoxy)-pyrimidine-5-carboxylic acid (2-methoxy-pyridin-3-yl)-methyl-amide

HRID 1025908Notes

Reaction equation

HRID 1025908 reaction equation
[Cl:1][C:2]1[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:3]=1[O:4][C:5]1[C:10]([C:11]([OH:13])=O)=[CH:9][N:8]=[CH:7][N:6]=1.[CH2:19](N(CC)CC)C.[I-].ClC1C=CC=C[N+]=1C.[CH3:35][O:36][C:37]1[C:42]([NH2:43])=[CH:41][CH:40]=[CH:39][N:38]=1.[H-].[Na+].CI>ClCCl>[CH3:35][O:36][C:37]1[C:42]([N:43]([CH3:19])[C:11]([C:10]2[C:5]([O:4][C:3]3[CH:14]=[C:15]([Cl:18])[CH:16]=[CH:17][C:2]=3[Cl:1])=[N:6][CH:7]=[N:8][CH:9]=2)=[O:13])=[CH:41][CH:40]=[CH:39][N:38]=1

Participants

8

Reactant 6

HCID 6328Methyl iodideHCID 8471TriethylamineHCID 24758Sodium hydrideHCID 1670692-Chloro-1-methylpyridinium iodideHCID 27374883-Amino-2-methoxypyridineHCID 673202614-(2,5-Dichloro-phenoxy)-pyrimidine-5-carboxylic acid

Product 1

HCID 533117024-(2,5-Dichloro-phenoxy)-pyrimidine-5-carboxylic acid (2-methoxy-pyridin-3-yl)-methyl-amideYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 50 mg (0.17 mmol) (4-(2,5-dichloro-phenoxy)-pyrimidine-5-carboxylic acid (Example 76, intermediate a) in 1.5 mL dichloromethane were added 0.05 mL (0.34 mmol) triethylamine and 49 mg (0.19 mmol) 2-chloro-1-methylpyridinium iodide. After stirring at room temperature for 20 minutes, 24 mg (0.19 mmol) 2-methoxypyridin-3-amine (commercially available, CAS RN 20265-38-7) were added. After 2 hours, the reaction mixture was poured on water and extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered and evaporated. The crude product was dissolved in 1 mL N,N-dimethylformamide and 14 mg (0.35 mmol) sodium hydride (60% suspension in mineral oil) followed by 0.02 mL (0.35 mmol) of methyliodide were added. The reaction was stirred at 50° C. for 2 hours. The suspension was filtered using a syringe micro filter and purified on a preparative HPLC system (Phenomenex Gemini column) using a gradient of acetonitrile:water (containing 0.05% formic acid) (10:90 to 98:2) to give 28 mg (39%) of the desired compound as a light brown solid. MS (ESI): m/z=405.0 [M+H]+.

Workup

  1. waitAfter 2 hours
  2. additionthe reaction mixture was poured on water
  3. extractionextracted with dichloromethane
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe crude product was dissolved in 1 mL N,N-dimethylformamide
  8. additionwere added
  9. stirringThe reaction was stirred at 50° C. for 2 hours
  10. filtrationThe suspension was filtered
  11. filtrationmicro filter
  12. custompurified on a preparative HPLC system (Phenomenex Gemini column)

Sources & evidence

ORD record
ord-73784f3a89bc4902b9c79aa58a65dfda
Source dataset
uspto-grants-2014_05
Patent number
US08729091B2

Reaction notes

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