Trifluoroacetic acid → HCID 89933989, compound

HRID 921741Notes

Reaction equation

HRID 921741 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([NH:22][C:23]2[N:28]=[C:27]([N:29](CC)[CH2:30][C:31]3C=CC(OC)=CC=3)[C:26]3=[N:41][CH:42]=[C:43]([C:44]#[N:45])[N:25]3[N:24]=2)[C:6]([F:21])=[C:7]([N:9]2[CH2:14][CH2:13][C@@H:12]([NH:15][C:16](=[O:19])[O:17][CH3:18])[C@H:11]([OH:20])[CH2:10]2)[CH:8]=1)#[N:2].C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>ClCCCl>[C:1]([C:3]1[CH:4]=[C:5]([NH:22][C:23]2[N:28]=[C:27]([NH:29][CH2:30][CH3:31])[C:26]3=[N:41][CH:42]=[C:43]([C:44]#[N:45])[N:25]3[N:24]=2)[C:6]([F:21])=[C:7]([N:9]2[CH2:14][CH2:13][C@@H:12]([NH:15][C:16](=[O:19])[O:17][CH3:18])[C@H:11]([OH:20])[CH2:10]2)[CH:8]=1)#[N:2]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 131732400HCID 131732400, compound

Product 1

HCID 89933989HCID 89933989, compoundYield 7.8%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
25 °C

Procedure

To methyl ((3R,4R)-1-(5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)-2-fluorophenyl)-3-hydroxypiperidin-4-yl)carbamate (60 mg, 0.098 mmol), in DCE (1.5 mL) was added ANISOLE (0.1 mL, 0.915 mmol) and TFA (1.0 mL, 12.98 mmol); the mixture stirred 2 h at 25° C. and solvent was removed. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×200 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: water with 20-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile: water with 20-mM ammonium acetate; Gradient: 15-100% 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 to afford methyl ((3R,4R)-1-(5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)-2-fluorophenyl)-3-hydroxypiperidin-4-yl)carbamate (3.8 mg).

Workup

  1. customsolvent was removed
  2. customThe crude material was purified via preparative LC/MS with the following conditions
  3. waitGradient: 15-100% 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-06fe2b9f06d44c58afc37f0c64f4c2df
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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