Trifluoroacetic acid → ethyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamate

HRID 921708Notes

Reaction equation

HRID 921708 reaction equation
[CH2:1]([O:3][C:4](=[O:46])[NH:5][C@@H:6]1[CH2:11][CH2:10][N:9]([C:12]2[CH:17]=[C:16]([C:18]#[N:19])[CH:15]=[C:14]([NH:20][C:21]3[N:26]=[C:25]([N:27](CC)[CH2:28][C:29]4C=CC(OC)=CC=4)[C:24]4=[N:39][CH:40]=[C:41]([C:42]#[N:43])[N:23]4[N:22]=3)[C:13]=2[Cl:44])[CH2:8][C@H:7]1[OH:45])[CH3:2].C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>ClCCCl>[Cl:44][C:13]1[C:14]([NH:20][C:21]2[N:26]=[C:25]([NH:27][CH2:28][CH3:29])[C:24]3=[N:39][CH:40]=[C:41]([C:42]#[N:43])[N:23]3[N:22]=2)=[CH:15][C:16]([C:18]#[N:19])=[CH:17][C:12]=1[N:9]1[CH2:10][CH2:11][C@@H:6]([NH:5][C:4](=[O:46])[O:3][CH2:1][CH3:2])[C@H:7]([OH:45])[CH2:8]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 131732396ethyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamate

Product 1

HCID 89932122ethyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamateYield 28%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
25 °C

Procedure

To ethyl((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamate (50 mg, 0.068 mmol), in DCE (0.8 mL) was added anisole (0.1 mL, 0.915 mmol) and TFA (0.5 mL, 6.49 mmol); the mixture stirred 2 h at 25° C. and solvent was removed. 2N NH3/MeOH (5 ml) was added and the mixture stirred for 30 min at 25° C. The solution was stored at −20° C. and a white precipitate formed. The material was collected by filtration, washed with 20 ml cold MeOH, 5 ml ether and dried under air-suction for 0.5 h to afford ethyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamate (10 mg).

Workup

  1. customsolvent was removed
  2. addition2N NH3/MeOH (5 ml) was added
  3. stirringthe mixture stirred for 30 min at 25° C
  4. customwas stored at −20° C.
  5. customa white precipitate formed
  6. filtrationThe material was collected by filtration
  7. washwashed with 20 ml cold MeOH, 5 ml ether
  8. customdried under air-suction for 0.5 h

Sources & evidence

ORD record
ord-ae29bb11076b4256bb6377c01b40219d
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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