Trifluoroacetic acid → (3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4-((methoxycarbonyl)amino)piperidin-3-yl 4-(phosphonooxy)butanoate

HRID 1430892Notes

Reaction equation

HRID 1430892 reaction equation
C([O:5][P:6]([O:13][CH2:14][CH2:15][CH2:16][C:17]([O:19][C@H:20]1[C@H:25]([NH:26][C:27]([O:29][CH3:30])=[O:28])[CH2:24][CH2:23][N:22]([C:31]2[CH:36]=[C:35]([C:37]#[N:38])[CH:34]=[C:33]([NH:39][C:40]3[N:45]=[C:44]([N:46](CC)[CH2:47][C:48]4C=CC(OC)=CC=4)[C:43]4=[N:58][CH:59]=[C:60]([C:61]#[N:62])[N:42]4[N:41]=3)[C:32]=2[Cl:63])[CH2:21]1)=[O:18])([O:8]C(C)(C)C)=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O.C1(OC)C=CC=CC=1>ClCCCl>[P:6]([O:13][CH2:14][CH2:15][CH2:16][C:17]([O:19][C@H:20]1[C@H:25]([NH:26][C:27]([O:29][CH3:30])=[O:28])[CH2:24][CH2:23][N:22]([C:31]2[CH:36]=[C:35]([C:37]#[N:38])[CH:34]=[C:33]([NH:39][C:40]3[N:45]=[C:44]([NH:46][CH2:47][CH3:48])[C:43]4=[N:58][CH:59]=[C:60]([C:61]#[N:62])[N:42]4[N:41]=3)[C:32]=2[Cl:63])[CH2:21]1)=[O:18])([OH:8])([OH:7])=[O:5]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 86708584(3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4-((methoxycarbonyl)amino)piperidin-3-yl 4-((di-tert-butoxyphosphoryl)oxy)butanoate

Product 1

HCID 86708587(3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4-((methoxycarbonyl)amino)piperidin-3-yl 4-(phosphonooxy)butanoateYield 7.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of (3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4-((methoxycarbonyl)amino)piperidin-3-yl 4-((di-tert-butoxyphosphoryl)oxy)butanoate (72 mg, 0.079 mmol) in DCE (2 mL) at 0° C. was added TFA (25% in DCE) (6.10 mL, 19.79 mmol) followed by anisole (0.035 mL, 0.317 mmol) and stirred at 35° C. for overnight. After completion of the starting material (by LC-MS), reaction was concentrated and purified by reverse phase preparative HPLC and collected fractions were lyophilized to give (3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4-((methoxycarbonyl)amino)piperidin-3-yl 4-(phosphonooxy)butanoate (4 mg) as an off white solid.

Workup

  1. customAfter completion of the starting material (by LC-MS), reaction
  2. concentrationwas concentrated
  3. custompurified by reverse phase preparative HPLC
  4. customcollected fractions

Sources & evidence

ORD record
ord-3ed2e17bc45b455c93a3d2fd709a52aa
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

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