Lithium Hexamethyldisilazide → 7-bromo-N-cyclopropyl-N-(4-methoxybenzyl)-2-(methylthio)imidazo[2,1-f][1,2,4]triazin-4-amine

HRID 921635Notes

Reaction equation

HRID 921635 reaction equation
[Br:1][C:2]1[N:10]2[C:5]([C:6](SC)=[N:7][C:8]([S:11][CH3:12])=[N:9]2)=[N:4][CH:3]=1.[CH3:15][O:16][C:17]1[CH:27]=[CH:26][C:20]([CH2:21][NH:22][CH:23]2[CH2:25][CH2:24]2)=[CH:19][CH:18]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Br:1][C:2]1[N:10]2[C:5]([C:6]([N:22]([CH:23]3[CH2:25][CH2:24]3)[CH2:21][C:20]3[CH:26]=[CH:27][C:17]([O:16][CH3:15])=[CH:18][CH:19]=3)=[N:7][C:8]([S:11][CH3:12])=[N:9]2)=[N:4][CH:3]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 4721289N-((4-methoxyphenyl)methyl)cyclopropanamineHCID 574576447-Bromo-2,4-bis(methylthio)imidazo[2,1-f][1,2,4]triazine

Product 1

HCID 867084907-bromo-N-cyclopropyl-N-(4-methoxybenzyl)-2-(methylthio)imidazo[2,1-f][1,2,4]triazin-4-amineYield 72.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a 25 mL flask was added a mixture of 7-bromo-2,4-bis(methylthio)imidazo[2,1-f][1,2,4]triazine (2.0 g, 6.87 mmol), N-(4-methoxybenzyl)cyclopropanamine (1.34 g, 7.56 mmol) in anhydrous THF (20 mL). The reaction solution was cooled to −78° C. and treated drop wise with 1.0 M lithium bis(trimethylsilyl)amide in THF solution (20.61 mL, 20.61 mmol, 3 eq, 1M solution in THF). The reaction was stirred at −78° C. for 1 hour, then allowed to come to room temperature and stirred for 3 hours. The reaction was quenched with saturated ammonium chloride. The product was extracted with ethyl acetate; the organic layer was dried with sodium sulfate and concentrated in vacuo. The crude product mixture was purified via ISCO (0-100% of ethyl acetate/heptane in 10 minutes, 24 g silica column) to give the pure product 7-bromo-N-cyclopropyl-N-(4-methoxybenzyl)-2-(methylthio)imidazo[2,1-f][1,2,4]triazin-4-amine (2.1 g)

Workup

  1. additionTo a 25 mL flask was added
  2. customto come to room temperature
  3. stirringstirred for 3 hours
  4. customThe reaction was quenched with saturated ammonium chloride
  5. extractionThe product was extracted with ethyl acetate
  6. dry with materialthe organic layer was dried with sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe crude product mixture was purified via ISCO (0-100% of ethyl acetate/heptane in 10 minutes, 24 g silica column)

Sources & evidence

ORD record
ord-0241e7bfde6149fe83388b0c20ecfbe3
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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