Trifluoroacetic acid → HCID 89922761, compound

HRID 921920Notes

Reaction equation

HRID 921920 reaction equation
[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]([CH3:22])[CH:15]3[CH2:19][C:18](=[O:20])[N:17]([CH3:21])[CH2:16]3)[CH2:10][CH2:9]2)=[CH:6][C:5]([C:23]#[N:24])=[CH:4][C:3]=1[NH:25][C:26]1[N:31]=[C:30]([N:32]([CH:42]2[CH2:44][CH2:43]2)CC2C=CC(OC)=CC=2)[C:29]2=[N:45][CH:46]=[C:47]([C:48]#[N:49])[N:28]2[N:27]=1.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[C:7]([N:8]2[CH2:9][CH2:10][CH:11]([N:14]([CH3:22])[CH:15]3[CH2:19][C:18](=[O:20])[N:17]([CH3:21])[CH2:16]3)[CH2:12][CH2:13]2)=[CH:6][C:5]([C:23]#[N:24])=[CH:4][C:3]=1[NH:25][C:26]1[N:31]=[C:30]([NH:32][CH:42]2[CH2:44][CH2:43]2)[C:29]2=[N:45][CH:46]=[C:47]([C:48]#[N:49])[N:28]2[N:27]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 1182534382-((2-Chloro-5-cyano-3-(4-(methyl(1-methyl-5-oxopyrrolidin-3-yl)amino)piperidin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Product 1

HCID 89922761HCID 89922761, compoundYield 15.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a round bottom flask charged with 2-((2-chloro-5-cyano-3-(4-(methyl(1-methyl-5-oxopyrrolidin-3-yl)amino)piperidin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (36.1 mg, 0.053 mmol) in dichloromethane (265 μl) was added anisole (28.9 μl, 0.265 mmol) and trifluoroacetic acid (204 μl, 2.65 mmol). The reaction mixture was stirred at room temperature ON. Excess TFA was removed by concentration 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: 15-100% B over 20 minutes, then a 0-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-(4-(methyl(1-methyl-5-oxopyrrolidin-3-yl)amino)piperidin-1-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (4.5 mg) was isolated.

Workup

  1. customExcess TFA was removed by concentration in vacuo
  2. customThe crude material was purified via preparative LC/MS with the following conditions
  3. customa 0-minute hold
  4. additionFractions containing the desired product
  5. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-8fd2b64d67a144dfb1bd70181e63e0a3
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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