Trifluoroacetic acid → HCID 86708582, compound

HRID 1430890Notes

Reaction equation

HRID 1430890 reaction equation
COC1C=CC(C[O:8][C@@H:9]([CH3:57])[C:10]([O:12][C@H:13]2[C@H:18]([NH:19][C:20]([O:22][CH3:23])=[O:21])[CH2:17][CH2:16][N:15]([C:24]3[CH:29]=[C:28]([C:30]#[N:31])[CH:27]=[C:26]([NH:32][C:33]4[N:38]=[C:37]([N:39](CC)[CH2:40][C:41]5C=CC(OC)=CC=5)[C:36]5=[N:51][CH:52]=[C:53]([C:54]#[N:55])[N:35]5[N:34]=4)[C:25]=3[Cl:56])[CH2:14]2)=[O:11])=CC=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>ClCCCl>[OH:8][C@@H:9]([CH3:57])[C:10]([O:12][C@H:13]1[C@H:18]([NH:19][C:20]([O:22][CH3:23])=[O:21])[CH2:17][CH2:16][N:15]([C:24]2[CH:29]=[C:28]([C:30]#[N:31])[CH:27]=[C:26]([NH:32][C:33]3[N:38]=[C:37]([NH:39][CH2:40][CH3:41])[C:36]4=[N:51][CH:52]=[C:53]([C:54]#[N:55])[N:35]4[N:34]=3)[C:25]=2[Cl:56])[CH2:14]1)=[O:11]

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 86708583HCID 86708583, compound

Product 1

HCID 86708582HCID 86708582, compoundYield 14.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of (S)-(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 2-((4-methoxybenzyl)oxy)propanoate (0.050 g, 0.061 mmol) in DCE (3 mL) was added anisole (0.027 ml, 0.243 mmol) followed by TFA (25% in DCE) (4.68 mL, 15.18 mmol) and stirred at 35° C. for overnight. The reaction mixture was concentrated at 30° C. and resultant residue was washed with diethylether to give solid and this was purified by reverse phase preparative HPLC and collected fractions were lyophilized to give (S)-(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 2-hydroxypropanoate (0.005 g) as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated at 30° C.
  2. washresultant residue was washed with diethylether
  3. customto give solid
  4. customthis was purified by reverse phase preparative HPLC
  5. customcollected fractions

Sources & evidence

ORD record
ord-ff7fa026a78542e6bd7ad15bf3b959a5
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

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