Trifluoroacetic acid → HCID 89923215, compound

HRID 921914Notes

Reaction equation

HRID 921914 reaction equation
[CH2:1]([NH:3][C:4](=[O:47])[O:5][CH2:6][CH:7]1[O:12][CH2:11][CH2:10][N:9]([C:13]2[CH:18]=[C:17]([C:19]#[N:20])[CH:16]=[C:15]([NH:21][C:22]3[N:27]=[C:26]([N:28]([CH:38]4[CH2:40][CH2:39]4)CC4C=CC(OC)=CC=4)[C:25]4=[N:41][CH:42]=[C:43]([C:44]#[N:45])[N:24]4[N:23]=3)[C:14]=2[Cl:46])[CH2:8]1)[CH3:2].C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>ClCCl>[CH2:1]([NH:3][C:4](=[O:47])[O:5][CH2:6][CH:7]1[O:12][CH2:11][CH2:10][N:9]([C:13]2[CH:18]=[C:17]([C:19]#[N:20])[CH:16]=[C:15]([NH:21][C:22]3[N:27]=[C:26]([NH:28][CH:38]4[CH2:39][CH2:40]4)[C:25]4=[N:41][CH:42]=[C:43]([C:44]#[N:45])[N:24]4[N:23]=3)[C:14]=2[Cl:46])[CH2:8]1)[CH3:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 131734951(+/-)-(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)morpholin-2-yl)methyl ethylcarbamate

Product 1

HCID 89923215HCID 89923215, compoundYield 21.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a vial charged with (+/−)-(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)morpholin-2-yl)methyl ethylcarbamate (33.5 mg, 0.051 mmol) in dichlorornethane (204 μl) was added anisole (27.9 μl, 0.255 mmol), followed by trifluoroacetic acid (157 μl, 2.040 mmol). The reaction mixture was stirred at room temperature ON. Excess TFA was removed by concentration in vacuo. The crude residue was taken up in methanol and free based using a 1 g Phenomenex Strata SCX 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, 19×250 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: 15-100% B over 15 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. (+/−)-(4-(2-Chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)morpholin-2-yl)methyl ethylcarbamate (5.9 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. customa 5-minute hold
  6. additionFractions containing the desired product
  7. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-4bbb9efb096542d09c4cacdf5f06837a
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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