Methyl iodide → N-methyl-N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1, 2, 4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)cyclopropanesulfonamide

HRID 2204511Notes

Reaction equation

HRID 2204511 reaction equation
[H-].[Na+].[S:3]([N:13]1[C:17]2[N:18]=[CH:19][C:20]3[N:21]([C:22]([C:25]45[CH2:32][CH2:31][C:28]([NH:33][S:34]([CH:37]6[CH2:39][CH2:38]6)(=[O:36])=[O:35])([CH2:29][CH2:30]4)[CH2:27][CH2:26]5)=[N:23][N:24]=3)[C:16]=2[CH:15]=[CH:14]1)([C:6]1[CH:12]=[CH:11][C:9]([CH3:10])=[CH:8][CH:7]=1)(=[O:5])=[O:4].I[CH3:41]>CN(C=O)C>[CH3:41][N:33]([C:28]12[CH2:27][CH2:26][C:25]([C:22]3[N:21]4[C:16]5[CH:15]=[CH:14][N:13]([S:3]([C:6]6[CH:7]=[CH:8][C:9]([CH3:10])=[CH:11][CH:12]=6)(=[O:4])=[O:5])[C:17]=5[N:18]=[CH:19][C:20]4=[N:24][N:23]=3)([CH2:30][CH2:29]1)[CH2:32][CH2:31]2)[S:34]([CH:37]1[CH2:38][CH2:39]1)(=[O:36])=[O:35]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58009845N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)cyclopropanesulfonamide

Product 1

HCID 58010192N-methyl-N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1, 2, 4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)cyclopropanesulfonamideYield 45.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

A round bottom flask was charged with sodium hydride (60% dispersion in mineral oil, 0.013 g, 0.33 mmol) and DMF (1 mL) to give a white suspension. The suspension was cooled to about 0° C. followed by the addition of a solution of N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)cyclopropanesulfonamide (0.15 g, 0.27 mmol, Example #7, Step C) in DMF (2 mL). The reaction mixture was stirred for about 15 min and iodomethane (0.06 g, 0.41 mmol) was added. The reaction mixture was stirred at about 0° C. for about 30 min, warmed to room temperature, and stirring was continued for about 2 h. The solvent was removed under reduced pressure. The residue was dissolved in DCM (5 mL) then purified by flash silica gel chromatography using EtOAc as the eluant to give N-methyl-N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)cyclopropanesulfonamide (0.068 g, 45%) as a yellow solid: LC/MS (Table 1, Method a) Rt=2.35 min; LC/MS m/z 555 (M+H)+.

Workup

  1. customto give a white suspension
  2. stirringThe reaction mixture was stirred at about 0° C. for about 30 min
  3. temperaturewarmed to room temperature
  4. stirringstirring
  5. waitwas continued for about 2 h
  6. customThe solvent was removed under reduced pressure
  7. dissolutionThe residue was dissolved in DCM (5 mL)
  8. customthen purified by flash silica gel chromatography

Sources & evidence

ORD record
ord-d315f03193d04941b1d79ca66f09d28c
Source dataset
uspto-grants-2016_06
Patent number
US09365579B2

Reaction notes

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