Trifluoroacetic acid → HCID 89922735, compound

HRID 921923Notes

Reaction equation

HRID 921923 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[C:9]([CH3:15])=[N:10][N:11]([CH3:14])[C:12]=2[CH3:13])=[CH:6][C:5]([C:16]#[N:17])=[CH:4][C:3]=1[NH:18][C:19]1[N:24]=[C:23]([N:25]([CH:35]2[CH2:37][CH2:36]2)CC2C=CC(OC)=CC=2)[C:22]2=[N:38][CH:39]=[C:40]([C:41]#[N:42])[N:21]2[N:20]=1.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[C:7]([C:8]2[C:9]([CH3:15])=[N:10][N:11]([CH3:14])[C:12]=2[CH3:13])=[CH:6][C:5]([C:16]#[N:17])=[CH:4][C:3]=1[NH:18][C:19]1[N:24]=[C:23]([NH:25][CH:35]2[CH2:37][CH2:36]2)[C:22]2=[N:38][CH:39]=[C:40]([C:41]#[N:42])[N:21]2[N:20]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 899229142-((2-Chloro-5-cyano-3-(1,3,5-trimethyl-1H-pyrazol-4-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Product 1

HCID 89922735HCID 89922735, compoundYield 33.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a round bottom flask charged with 2-((2-chloro-5-cyano-3-(1,3,5-trimethyl-1H-pyrazol-4-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (30 mg, 0.052 mmol) in dichloromethane (345 μl) was added anisole (22.64 μl, 0.207 mmol), followed by trifluoroacetic acid (200 μl, 2.59 mmol). The reaction mixture was stirred at room temperature 2 d. Excess TFA was removed by concentration in vacuo. The crude residue was taken up in methanol and free based using a Phenomenex Strata SCX 1 g column. The column was flushed with 3 column volumes MeOH and 1 column volume 7 N NH3/MeOH. The ammonia containing fraction was concentrated in vacuo. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×200 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile: water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 10-mM ammonium acetate; Gradient: 20-100% B over 20 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. 2-((2-Chloro-5-cyano-3-(1,3,5-trimethyl-1H-pyrazol-4-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (8 mg) was isolated.

Workup

  1. customExcess TFA was removed by concentration in vacuo
  2. customThe column was flushed with 3 column volumes MeOH and 1 column volume 7 N NH3/MeOH
  3. concentrationThe ammonia containing fraction was concentrated in vacuo
  4. customThe crude material was purified via preparative LC/MS with the following conditions
  5. waitGradient: 20-100% B over 20 minutes
  6. customa 5-minute hold
  7. additionFractions containing the desired product
  8. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-54410380c89044479cf31bb7462a7be7
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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