Trifluoroacetic acid → HCID 89923886, compound

HRID 921939Notes

Reaction equation

HRID 921939 reaction equation
C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[C:14]([NH:15][C:16]2[N:21]=[C:20]([N:22]([CH:32]3[CH2:34][CH2:33]3)CC3C=CC(OC)=CC=3)[C:19]3=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]3[N:17]=2)=[CH:13][C:12]([C:40]#[N:41])=[CH:11][C:10]=1[N:42]1[CH2:50][C@H:49]2[C@H:44]([N:45](C(OC(C)(C)C)=O)[CH2:46][CH2:47][CH2:48]2)[CH2:43]1.C1(OC)C=CC=CC=1>ClCCCl>[Cl:8][C:9]1[C:10]([N:42]2[CH2:50][C@H:49]3[C@H:44]([NH:45][CH2:46][CH2:47][CH2:48]3)[CH2:43]2)=[CH:11][C:12]([C:40]#[N:41])=[CH:13][C:14]=1[NH:15][C:16]1[N:21]=[C:20]([NH:22][CH:32]2[CH2:33][CH2:34]2)[C:19]2=[N:35][CH:36]=[C:37]([C:38]#[N:39])[N:18]2[N:17]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 118253431HCID 118253431, compound

Product 1

HCID 89923886HCID 89923886, compoundYield 69.9%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

TFA (0.382 mL, 4.96 mmol) was added to a solution of (4aS,7aS)-tert-butyl 6-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)octahydro-1H-pyrrolo[3,4-b]pyridine-1-carboxylate (50 mg, 0.072 mmol) and anisole (0.031 mL, 0.288 mmol) in DCE (1 mL) and the reaction mixture was heated at 60° C. for 1 hour. The solvent was removed in vacuo and the material azeotroped with toluene 3× to remove the excess TFA. 10 ml of 2N NH3 in MeOH was added, and the solution was stirred for 20 min. The solvent was removed in vacuo and the material was triturated with MeOH/Et2O (1:20 ratio). The solid was collected by vacuum filtration to give a yellow solid which was purified by prep-HPLC to give 2-((2-chloro-5-cyano-3-((4aS,7aS)-hexahydro-1H-pyrrolo[3,4-b]pyridin-6(2H)-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (23.9 mg)

Workup

  1. customThe solvent was removed in vacuo
  2. customthe material azeotroped with toluene 3×
  3. customto remove the excess TFA
  4. addition10 ml of 2N NH3 in MeOH was added
  5. customThe solvent was removed in vacuo
  6. customthe material was triturated with MeOH/Et2O (1:20 ratio)
  7. filtrationThe solid was collected by vacuum filtration
  8. customto give a yellow solid which
  9. customwas purified by prep-HPLC

Sources & evidence

ORD record
ord-01d77216370946dda7141b1dd9ebf1bc
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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