Trifluoroacetic acid → HCID 86708538, compound

HRID 1430850Notes

Reaction equation

HRID 1430850 reaction equation
[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][O:11][CH:10]([C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[O:15])[CH2:9]2)=[CH:6][C:5]([C:22]#[N:23])=[CH:4][C:3]=1[NH:24][C:25]1[N:30]=[C:29]([N:31]([CH:41]2[CH2:43][CH2:42]2)CC2C=CC(OC)=CC=2)[C:28]2=[N:44][CH:45]=[C:46]([C:47]#[N:48])[N:27]2[N:26]=1.C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>ClCCl>[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][O:11][CH:10]([C:14]([N:16]3[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)=[O:15])[CH2:9]2)=[CH:6][C:5]([C:22]#[N:23])=[CH:4][C:3]=1[NH:24][C:25]1[N:30]=[C:29]([NH:31][CH:41]2[CH2:43][CH2:42]2)[C:28]2=[N:44][CH:45]=[C:46]([C:47]#[N:48])[N:27]2[N:26]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid3×HCID 7519AnisoleHCID 867085392-((2-Chloro-5-cyano-3-(2-(morpholine-4-carbonyl)morpholino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Product 1

HCID 86708538HCID 86708538, compoundYield 24.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a round bottom flask charged with 2-((2-chloro-5-cyano-3-(2-(morpholine-4-carbonyl)morpholino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (64.9 mg, 0.097 mmol) in dichloromethane (485 μl) was added anisole (21.19 μl, 0.194 mmol), followed by TFA (224 μl, 2.91 mmol). The reaction mixture was stirred at rt ON. Additional TFA (224 μl, 2.91 mmol) was added. Stir at rt ON. Additional TFA (224 μl, 2.91 mmol) was added and the reaction mixture was stirred at rt ON. Excess TFA was removed by concentration in vacuo. The crude residue was taken up in methanol and free based using a Phenomenex Strata 1 g SCX column. The column was flushed with 3 column volumes methanol and 3 column volumes 3.5 N ammonia/methanol. The ammonia layers were concentrated in vacuo. The crude material was purified by neutral phase preparatory LC/MS chromatography to provide (+/−) 2-((2-chloro-5-cyano-3-(2-(morpholine-4-carbonyl)morpholino)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (13 mg).

Workup

  1. stirringStir at rt ON
  2. stirringthe reaction mixture was stirred at rt ON
  3. customExcess TFA was removed by concentration in vacuo
  4. customThe column was flushed with 3 column volumes methanol and 3 column volumes 3.5 N ammonia/methanol
  5. concentrationThe ammonia layers were concentrated in vacuo
  6. customThe crude material was purified by neutral phase preparatory LC/MS chromatography

Sources & evidence

ORD record
ord-34b85378470e4f4ba21bbf030cab25e5
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

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