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 1430797Notes

Reaction equation

HRID 1430797 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 rt 2 d. The reaction mixture was warmed to 45° C. for 1 h. The reaction mixture was cooled to rt and concentrated in vacuo. After cooling to rt, 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 rt
  3. concentrationconcentrated in vacuo
  4. temperatureAfter cooling to rt
  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-60fc29a572d349ba91db5b60ee2c01fd
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

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