Methyl iodide → HCID 90203950, compound

HRID 1480229Notes

Reaction equation

HRID 1480229 reaction equation
[CH:1]1([C:4]2[C:5]([O:24][CH2:25][C:26]([F:29])([F:28])[F:27])=[CH:6][C:7]([C:10]([NH:12][C:13]([CH3:23])([C:18]3[N:19]=[N:20][NH:21][N:22]=3)[CH2:14][CH:15]3[CH2:17][CH2:16]3)=[O:11])=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[C:30](=O)([O-])[O-].[K+].[K+].IC>CN(C=O)C.C(OCC)(=O)C>[CH:1]1([C:4]2[C:5]([O:24][CH2:25][C:26]([F:27])([F:28])[F:29])=[CH:6][C:7]([C:10]([NH:12][C:13]([CH3:23])([C:18]3[N:22]=[N:21][N:20]([CH3:30])[N:19]=3)[CH2:14][CH:15]3[CH2:17][CH2:16]3)=[O:11])=[N:8][CH:9]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 76281462HCID 76281462, compound

Product 1

HCID 90203950HCID 90203950, compoundYield 39%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-cyclopropyl-N-[2-cyclopropyl-1-methyl-1-(2H-tetrazol-5-yl)ethyl]-4-(2,2,2-trifluoroethoxy)pyridine-2-carboxamide (example 150b, 100 mg, 0.244 mmol) in dry DMF (1.2 ml) was added potassium carbonate (43.8 mg, 0.317 mmol). The reaction mixture was stirred at room temperature for 10 minutes followed by addition of iodomethane (30.5 μl, 0.487 mmol). The reaction mixture was then stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and extracted with water and brine. The organic phase was dried over sodium sulfate and evaporated down to dryness. The crude material was purified by preparative HPLC to yield the title compound (40 mg, 39%) and also a second by-product as the regioisomer (11 mg, 10.6%). MS (ESI, m/z): 425.5 (M+H+).

Workup

  1. stirringThe reaction mixture was then stirred at room temperature overnight
  2. extractionextracted with water and brine
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. customevaporated down to dryness
  5. customThe crude material was purified by preparative HPLC

Sources & evidence

ORD record
ord-2dde36f9efc54b45856c22f9aa820353
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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