Trifluoroacetic acid → HCID 89931420, compound

HRID 921668Notes

Reaction equation

HRID 921668 reaction equation
[Cl:1][C:2]1[C:7]([NH:8][C:9]2[N:14]=[C:13]([N:15]([CH:25]3[CH2:27][CH2:26]3)CC3C=CC(OC)=CC=3)[C:12]3=[N:28][CH:29]=[C:30]([C:31]#[N:32])[N:11]3[N:10]=2)=[CH:6][C:5]([C:33]#[N:34])=[CH:4][C:3]=1[N:35]1[CH2:40][CH2:39][C@@H:38]([NH:41][C:42](=[O:45])[O:43][CH3:44])[C@H:37]([O:46][P:47]([OH:50])([OH:49])=[O:48])[CH2:36]1.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][CH:25]3[CH2:27][CH2:26]3)[C:12]3=[N:28][CH:29]=[C:30]([C:31]#[N:32])[N:11]3[N:10]=2)=[CH:6][C:5]([C:33]#[N:34])=[CH:4][C:3]=1[N:35]1[CH2:40][CH2:39][C@@H:38]([NH:41][C:42](=[O:45])[O:43][CH3:44])[C@H:37]([O:46][P:47]([OH:50])([OH:49])=[O:48])[CH2:36]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 131732390HCID 131732390, compound

Product 1

HCID 89931420HCID 89931420, compoundYield 55.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of methyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-(phosphonooxy)piperidin-4 yl)carbamate (0.007 g, 0.009 mmol) in DCE (1 mL) was added anisole (0.006 mL, 0.055 mmol) followed by TFA (25% in DCE) (1.1 mL, 3.57 mmol) and at 35° C. for overnight. After completion of starting material (by LCMS), reaction mixture was concentrated and residue was taken in DCM (5 mL) concentrated under vacuum, the same thing was repeated one more time with 5 mL DCM. The resultant mixture was purified by reverse phase preparative HPLC and collected fractions were lyophilized to give methyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-(phosphonooxy)piperidin-4 yl)carbamate (0.003 g) as white solid.

Workup

  1. customAfter completion of starting material (by LCMS), reaction mixture
  2. concentrationwas concentrated
  3. concentrationconcentrated under vacuum
  4. customThe resultant mixture was purified by reverse phase preparative HPLC
  5. customcollected fractions

Sources & evidence

ORD record
ord-8f050d70d3cb4c4aae0bbc8339510430
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

Loading…