Trifluoroacetic acid → HCID 89922442, compound

HRID 921808Notes

Reaction equation

HRID 921808 reaction equation
C(O)(C(F)(F)F)=O.[Cl:8][C:9]1[C:14]([O:15][CH2:16][C@@H:17]2[CH2:22][O:21][CH2:20][CH2:19][N:18]2CC2C=CC(OC)=CC=2OC)=[CH:13][C:12]([C:34]#[N:35])=[CH:11][C:10]=1[NH:36][C:37]1[N:42]=[C:41]([N:43]([CH:53]2[CH2:55][CH2:54]2)CC2C=CC(OC)=CC=2)[C:40]2=[N:56][CH:57]=[C:58]([C:59]#[N:60])[N:39]2[N:38]=1.C1(OC)C=CC=CC=1>ClC(Cl)C>[Cl:8][C:9]1[C:14]([O:15][CH2:16][C@@H:17]2[CH2:22][O:21][CH2:20][CH2:19][NH:18]2)=[CH:13][C:12]([C:34]#[N:35])=[CH:11][C:10]=1[NH:36][C:37]1[N:42]=[C:41]([NH:43][CH:53]2[CH2:54][CH2:55]2)[C:40]2=[N:56][CH:57]=[C:58]([C:59]#[N:60])[N:39]2[N:38]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 89923091HCID 89923091, compound

Product 1

HCID 89922442HCID 89922442, compoundYield 68.9%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
60 °C

Procedure

50% TFA in dichloroethane (1 ml) was added to a solution of (S)-2-((2-chloro-5-cyano-3-((4-(2,4-dimethoxybenzyl)morpholin-3-yl)methoxy)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (80 mg, 0.109 mmol) and anisole (0.095 ml, 0.869 mmol) in a 1-dram vial and the reaction mixture was heated at 60° C. for 4 hours. The reaction mixture was concentrated and residue was dried under vacuum overnight. The crude was dissolved in acetonitrile (2 ml) and neutralized with 2N ammonia in methanol (2 ml); white precipitate formed and was collected by filtration. This material was further purified by flash chromatography on silica gel using an automated ISCO system (24 g gold column, eluting with 1-6% 2 N ammonia in methanol/dichloromethane). (S)-2-((2-chloro-5-cyano-3-(morpholin-3-ylmethoxy)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (35 mg) was obtained as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customresidue was dried under vacuum overnight
  3. dissolutionThe crude was dissolved in acetonitrile (2 ml)
  4. customwhite precipitate formed
  5. filtrationwas collected by filtration
  6. customThis material was further purified by flash chromatography on silica gel using
  7. washan automated ISCO system (24 g gold column, eluting with 1-6% 2 N ammonia in methanol/dichloromethane)

Sources & evidence

ORD record
ord-053fc842f1d040bd800882cc1695d8b0
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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