7-bromo-2-chloro-N-ethyl-N-(4-methoxybenzyl)imidazo[2,1-f][1,2,4]triazin-4-amine → 2-Chloro-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 1430793Notes

Reaction equation

HRID 1430793 reaction equation
Br[C:2]1[N:10]2[C:5]([C:6]([N:12]([CH2:22][CH3:23])[CH2:13][C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)=[N:7][C:8]([Cl:11])=[N:9]2)=[N:4][CH:3]=1.[Cu][C:25]#[N:26]>CN1C(=O)CCC1>[Cl:11][C:8]1[N:7]=[C:6]([N:12]([CH2:22][CH3:23])[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[C:5]2=[N:4][CH:3]=[C:2]([C:25]#[N:26])[N:10]2[N:9]=1

Participants

4

Reactant 2

HCID 867084717-bromo-2-chloro-N-ethyl-N-(4-methoxybenzyl)imidazo[2,1-f][1,2,4]triazin-4-amineHCID 178418546HCID 178418546, compound

Product 1

HCID 867084732-Chloro-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileYield 101.9%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
25 °C

Procedure

(I10B): To an oven dried 500 ml round bottom flask was added 7-bromo-2-chloro-N-ethyl-N-(4-methoxybenzyl)imidazo[2,1-f][1,2,4]triazin-4-amine (12.5 g, 31.5 mmol) and copper(i) cyanide (9.0 g, 100 mmol). The flask was caped under nitrogen and NMP (250 mL) was added. The mixture stirred 5 min at 25° C. and the flask was evacuated and back-filled with nitrogen 3×. The reaction stirred at 135° C. (oil bath) 21 hr. The reaction cooled to 25° C., diluted with ethyl acetate (500 ml) and filter through edit bed. The bed was washed with EtoAc 3×100 ml and the filtrate washed with water 1×300 ml and brine 3×150 ml. The organics dried with sodium sulphate and remove solvent. The material was crystallized from IPA and filtered to afford 2-chloro-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (11 g).

Workup

  1. custom(I10B): To an oven dried 500 ml round bottom flask
  2. customThe flask was caped under nitrogen
  3. customthe flask was evacuated
  4. additionback-filled with nitrogen 3×
  5. stirringThe reaction stirred at 135° C. (oil bath) 21 hr
  6. temperatureThe reaction cooled to 25° C.
  7. additiondiluted with ethyl acetate (500 ml)
  8. filtrationfilter through edit bed
  9. washThe bed was washed with EtoAc 3×100 ml
  10. washthe filtrate washed with water 1×300 ml and brine 3×150 ml
  11. dry with materialThe organics dried with sodium sulphate
  12. customremove solvent
  13. customThe material was crystallized from IPA
  14. filtrationfiltered

Sources & evidence

ORD record
ord-c5b0ea3482774f39a5f62bede9270c20
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

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