Trifluoroacetic acid → 2-((3-(4-Aminopiperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921626Notes

Reaction equation

HRID 921626 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([N:15]([CH:25]3[CH2:27][CH2:26]3)CC3C=CC(OC)=CC=3)[C:12]3=[N:28][CH:29]=[C:30]([C:31]#[N:32])[N:11]3[N:10]=2)=[CH:6][C:5]([C:33]#[N:34])=[CH:4][C:3]=1[N:35]1[CH2:40][CH2:39][CH:38]([NH:41]C(=O)OC(C)(C)C)[CH2:37][CH2:36]1.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>ClCCl>[NH2:41][CH:38]1[CH2:37][CH2:36][N:35]([C:3]2[C:2]([Cl:1])=[C:7]([NH:8][C:9]3[N:14]=[C:13]([NH:15][CH:25]4[CH2:27][CH2:26]4)[C:12]4=[N:28][CH:29]=[C:30]([C:31]#[N:32])[N:11]4[N:10]=3)[CH:6]=[C:5]([C:33]#[N:34])[CH:4]=2)[CH2:40][CH2:39]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 86708476tert-Butyl (1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)carbamate

Product 1

HCID 867084792-((3-(4-Aminopiperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a round bottom flask charged with tert-butyl (1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)carbamate (I12C) (0.517 g, 0.773 mmol) in dichloromethane (5.15 ml) was added anisole (1.688 ml, 15.45 mmol), followed by the slow addition of trifluoroacetic acid (2.381 ml, 30.9 mmol). The reaction mixture was stirred at room temperature 2 d. The reaction mixture was warmed to 45° C. for 1 h. The reaction mixture was cooled to room temperature and concentrated in vacuo. After cooling to room temperature, 25 mL 2 N ammonia/methanol was added and a white solid crashed out of solution. The slurry was stirred for 30 min and the solid was isolated by vacuum filtration washing with cold methanol. 2-((3-(4-Aminopiperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (0.1563 g) was isolated as a white solid. Material used as is in subsequent transformations.

Workup

  1. temperatureThe reaction mixture was warmed to 45° C. for 1 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. temperatureAfter cooling to room temperature
  5. addition25 mL 2 N ammonia/methanol was added
  6. stirringThe slurry was stirred for 30 min
  7. customthe solid was isolated by vacuum filtration
  8. washwashing with cold methanol

Sources & evidence

ORD record
ord-82473ba447b84645bac82668b06cc8d0
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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