Potassium Carbonate → (+/-)-2-((2-Chloro-5-cyano-3-(2-(((4-methoxybenzyl)amino)methyl)morpholino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921916Notes

Reaction equation

HRID 921916 reaction equation
CS(O[CH2:6][CH:7]1[O:12][CH2:11][CH2:10][N:9]([C:13]2[CH:18]=[C:17]([C:19]#[N:20])[CH:16]=[C:15]([NH:21][C:22]3[N:27]=[C:26]([N:28]([CH:38]4[CH2:40][CH2:39]4)[CH2:29][C:30]4[CH:35]=[CH:34][C:33]([O:36][CH3:37])=[CH:32][CH:31]=4)[C:25]4=[N:41][CH:42]=[C:43]([C:44]#[N:45])[N:24]4[N:23]=3)[C:14]=2[Cl:46])[CH2:8]1)(=O)=O.[CH3:47][O:48][C:49]1[CH:56]=[CH:55][C:52]([CH2:53][NH2:54])=[CH:51][CH:50]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O.C(OCC)(=O)C>[Cl:46][C:14]1[C:13]([N:9]2[CH2:10][CH2:11][O:12][CH:7]([CH2:6][NH:54][CH2:53][C:52]3[CH:55]=[CH:56][C:49]([O:48][CH3:47])=[CH:50][CH:51]=3)[CH2:8]2)=[CH:18][C:17]([C:19]#[N:20])=[CH:16][C:15]=1[NH:21][C:22]1[N:27]=[C:26]([N:28]([CH:38]2[CH2:40][CH2:39]2)[CH2:29][C:30]2[CH:31]=[CH:32][C:33]([O:36][CH3:37])=[CH:34][CH:35]=2)[C:25]2=[N:41][CH:42]=[C:43]([C:44]#[N:45])[N:24]2[N:23]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 754524-MethoxybenzylamineHCID 89923151HCID 89923151, compound

Product 1

HCID 89923206(+/-)-2-((2-Chloro-5-cyano-3-(2-(((4-methoxybenzyl)amino)methyl)morpholino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileYield 64.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A vial was charged with (+/−)-(4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)morpholin-2-yl)methyl methanesulfonate (56.5 mg, 0.085 mmol) and 4-methoxybenzylamine (33.3 μl, 0.255 mmol) in acetonitrile (904 μl). Potassium carbonate (58.7 mg, 0.425 mmol) was added and the vial was capped and heated at 80° C. ON. After cooling to room temperature, the reaction mixture was diluted with water and ethyl acetate. The aqueous layer was extracted with ethyl acetate (3×). The combined organics were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. (+/−)-2-((2-Chloro-5-cyano-3-(2-(((4-methoxybenzyl)amino)methyl)morpholino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (38.9 mg) was isolated as a white solid and used as is in subsequent chemistry.

Workup

  1. customthe vial was capped
  2. temperatureAfter cooling to room temperature
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×)
  4. dry with materialThe combined organics were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d61fa13ea78c4b6387f71cacabffbe03
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

Loading…