Trifluoroacetic acid → HCID 89922558, compound

HRID 921964Notes

Reaction equation

HRID 921964 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([N:15](CC)[CH2:16][C:17]3C=CC(OC)=CC=3)[C:12]3=[N:27][CH:28]=[C:29]([C:30]#[N:31])[N:11]3[N:10]=2)=[CH:6][C:5]([C:32]#[N:33])=[CH:4][C:3]=1[NH:34][C@@H:35]1[CH2:40][CH2:39][N:38]([C:41]([O:43][CH3:44])=[O:42])[CH2:37][C@H:36]1[OH:45].C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>ClCCCl>[Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([NH:15][CH2:16][CH3:17])[C:12]3=[N:27][CH:28]=[C:29]([C:30]#[N:31])[N:11]3[N:10]=2)=[CH:6][C:5]([C:32]#[N:33])=[CH:4][C:3]=1[NH:34][C@@H:35]1[CH2:40][CH2:39][N:38]([C:41]([O:43][CH3:44])=[O:42])[CH2:37][C@H:36]1[OH:45]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 89923930HCID 89923930, compound

Product 1

HCID 89922558HCID 89922558, compoundYield 20.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
40 °C

Procedure

To (3R,4R)-methyl 4-((2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)amino)-3-hydroxypiperidine-1-carboxylate (30.9 mg, 0.049 mmol) was added DCE (3 mL), anisole (5.35 μl, 0.049 mmol) and TFA (0.5 mL, 6.49 mmol); the reaction stirred 2 hr at 40° C. and solvents removed. The crude material was purified via preparative LC/MS with the following conditions: Column: 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: 10-60% 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 to afford (3R,4R)-methyl 4-((2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)amino)-3-hydroxypiperidine-1-carboxylate (5.1 mg).

Workup

  1. customsolvents removed
  2. customThe crude material was purified via preparative LC/MS with the following conditions
  3. waitGradient: 10-60% B over 20 minutes
  4. customa 5-minute hold
  5. additionFractions containing the desired product
  6. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-dae42c7eaab64ba49090c40cc3b814f3
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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