2,6-Lutidine → HCID 89923475, compound

HRID 921826Notes

Reaction equation

HRID 921826 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[C:18]([C:20]#[N:21])[CH:17]=[C:16]([NH:22][C:23]3[N:28]=[C:27]([N:29]([CH:39]4[CH2:41][CH2:40]4)CC4C=CC(OC)=CC=4)[C:26]4=[N:42][CH:43]=[C:44]([C:45]#[N:46])[N:25]4[N:24]=3)[C:15]=2[Cl:47])[CH2:10][CH:9]1[C:48](=[O:52])[N:49]([CH3:51])[CH3:50])=O)(C)(C)C.N1C(C)=CC=CC=1C.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>C(Cl)Cl>[Cl:47][C:15]1[C:16]([NH:22][C:23]2[N:28]=[C:27]([NH:29][CH:39]3[CH2:40][CH2:41]3)[C:26]3=[N:42][CH:43]=[C:44]([C:45]#[N:46])[N:25]3[N:24]=2)=[CH:17][C:18]([C:20]#[N:21])=[CH:19][C:14]=1[N:11]1[CH2:12][CH2:13][NH:8][CH:9]([C:48]([N:49]([CH3:51])[CH3:50])=[O:52])[CH2:10]1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 65367Trimethylsilyl triflateHCID 89922541Tert-butyl 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)-2-(dimethylcarbamoyl)piperazine-1-carboxylate

Product 1

HCID 89923475HCID 89923475, compoundYield 135.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Tert-butyl-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)-2-(dimethylcarbamoyl)piperazine-1-carboxylate (200 mg, 0.275 mmol) was taken up in DCM (2 mL) and cooled to 0° C. 2,6-Lutidine (0.096 mL, 0.826 mmol) was added, followed by drop wise addition of TMS-OTf (0.149 mL, 0.826 mmol). The reaction was stirred at 0° C. for 10 min, then brought to room temperature and stirred for 20 min. The reaction was quenched with 2M K3PO4 solution and extracted 2× with DCM. The organic layers were combined, dried over Na2SO4, filtered, and concentrated to give 188 mg of a yellow solid. The material was purified by flash column chromatography (0-70% 10% MeOH/DCM; 24 g column). 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)-N,N-dimethylpiperazine-2-carboxamide (133 mg) was obtained as a yellow solid.

Workup

  1. custombrought to room temperature
  2. stirringstirred for 20 min
  3. customThe reaction was quenched with 2M K3PO4 solution
  4. extractionextracted 2× with DCM
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-7e7a57c99dff43da9eb5efb0b82a69df
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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