Methyl iodide → Tert-butyl (6-chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)(methyl)carbamate

HRID 873975Notes

Reaction equation

HRID 873975 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[C:5]2[N:6]([C:8]([CH3:11])=[N:9][N:10]=2)[N:7]=1.[H-].[Na+].[CH3:22]I>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:12]([CH3:22])[C:13](=[O:19])[O:14][C:15]([CH3:16])([CH3:18])[CH3:17])[C:5]2[N:6]([C:8]([CH3:11])=[N:9][N:10]=2)[N:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 117714658Tert-butyl (6-chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate

Product 1

HCID 117714659Tert-butyl (6-chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)(methyl)carbamateYield 98.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of tert-butyl (6-chloro-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)carbamate (Step 112.4) (202 mg, 0.712 mmol) in DMF (4 mL) under Ar was added NaH (34.2 mg, 0.854 mmol) and the resulting mixture was stirred at RT for 30 min. MeI (0.053 mL, 0.854 mmol) was added to the mixture and stirred for further 30 min. The reaction was quenched with a saturated aq. NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with a saturated aq. NaHCO3 solution, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (hexane/EtOAc 25-40%) to afford the title product (208 mg, 0.699 mmol, 98% yield) as white solid. tR: 4.45 min (HPLC 1); tR: 1.00 min (LC-MS 2); ESI-MS: 298 [M+H]+ (LC-MS 2); Rf=0.45 (hexane/EtOAc 1:1).

Workup

  1. stirringstirred for further 30 min
  2. customThe reaction was quenched with a saturated aq. NaHCO3 solution
  3. extractionextracted with EtOAc
  4. washThe combined organic layers were washed with a saturated aq. NaHCO3 solution
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by silica gel column chromatography (hexane/EtOAc 25-40%)

Sources & evidence

ORD record
ord-6c04cbcea5894b508b56871072ae1292
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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