Methyl iodide → [(S)-1-(3-Bromo-imidazo[1,2-b]pyridazin-6-yl)-pyrrolidin-3-yl]-methyl-amine

HRID 870775Notes

Reaction equation

HRID 870775 reaction equation
C(O[C:6](=O)[NH:7][C@H:8]1[CH2:12][CH2:11][N:10]([C:13]2[CH:14]=[CH:15][C:16]3[N:17]([C:19]([Br:22])=[CH:20][N:21]=3)[N:18]=2)[CH2:9]1)(C)(C)C.IC.[H-].[Na+]>CN(C=O)C>[Br:22][C:19]1[N:17]2[N:18]=[C:13]([N:10]3[CH2:11][CH2:12][C@H:8]([NH:7][CH3:6])[CH2:9]3)[CH:14]=[CH:15][C:16]2=[N:21][CH:20]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86696486[(S)-1-(3-Bromo-imidazo[1,2-b]pyridazin-6-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester

Product 1

HCID 86696485[(S)-1-(3-Bromo-imidazo[1,2-b]pyridazin-6-yl)-pyrrolidin-3-yl]-methyl-amineYield 103.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

[(S)-1-(3-Bromo-imidazo[1,2-b]pyridazin-6-yl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester (1.2 g, 3.1 mmol) taken up in 15 mL DMF and cooled to 0° C. in an ice bath. Iodomethane (342 uL, 5.42 mmol) added and stirred 5 minutes. Then sodium hydride 60% in oil (251 mg, 6.2 mmol) was slowly added. Reaction stirred 5 minutes at 0° C. then removed from ice bath and stirred 30 minutes at room temperature. Reaction was quenched with ice then extracted with ethyl acetate 2×. Ethyl acetate fractions combined dried over magnesium sulfate filtered reduce in vacuo. This was then taken up in 26 mL DCM and 4 mL TFA added. Stirred 1 hour until complete by LC/MS. Reaction washed with 1N NaOH, DCM layer removed dried over magnesium sulfate filtered, reduced in vacuo to get 951 mg crude product carried on as is to part B. LRMS (ESI) m/z 296/298 [(M+H)]+, calc'd for C11H14BrN5: 296.17.

Workup

  1. customReaction
  2. stirringstirred 5 minutes at 0° C.
  3. customthen removed from ice bath
  4. stirringstirred 30 minutes at room temperature
  5. customReaction
  6. customwas quenched with ice
  7. extractionthen extracted with ethyl acetate 2×
  8. dry with materialEthyl acetate fractions combined dried over magnesium sulfate
  9. filtrationfiltered
  10. addition4 mL TFA added
  11. stirringStirred 1 hour until complete by LC/MS
  12. customReaction
  13. washwashed with 1N NaOH, DCM layer
  14. customremoved
  15. dry with materialdried over magnesium sulfate
  16. filtrationfiltered

Sources & evidence

ORD record
ord-f82e5c8340754524b27dffbf56f9e3d4
Source dataset
uspto-grants-2015_03
Patent number
US08969565B2

Reaction notes

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