Ethyl Acetate → (+/-)-2-((2-Chloro-5-cyano-3-(2-(hydroxymethyl)morpholino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921911Notes

Reaction equation

HRID 921911 reaction equation
[Si]([O:8][CH2:9][CH:10]1[CH2:15][N:14]([C:16]2[C:17]([Cl:49])=[C:18]([NH:24][C:25]3[N:30]=[C:29]([N:31]([CH:41]4[CH2:43][CH2:42]4)[CH2:32][C:33]4[CH:38]=[CH:37][C:36]([O:39][CH3:40])=[CH:35][CH:34]=4)[C:28]4=[N:44][CH:45]=[C:46]([C:47]#[N:48])[N:27]4[N:26]=3)[CH:19]=[C:20]([C:22]#[N:23])[CH:21]=2)[CH2:13][CH2:12][O:11]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Cl-].[NH4+].C(OCC)(=O)C>C1COCC1>[Cl:49][C:17]1[C:16]([N:14]2[CH2:13][CH2:12][O:11][CH:10]([CH2:9][OH:8])[CH2:15]2)=[CH:21][C:20]([C:22]#[N:23])=[CH:19][C:18]=1[NH:24][C:25]1[N:30]=[C:29]([N:31]([CH:41]2[CH2:43][CH2:42]2)[CH2:32][C:33]2[CH:34]=[CH:35][C:36]([O:39][CH3:40])=[CH:37][CH:38]=2)[C:28]2=[N:44][CH:45]=[C:46]([C:47]#[N:48])[N:27]2[N:26]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 89922952HCID 89922952, compound

Product 1

HCID 89922871(+/-)-2-((2-Chloro-5-cyano-3-(2-(hydroxymethyl)morpholino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrileYield 70.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To around bottom flask charged with (+/−)-2-((3-(2-(((tert-butyldimethylsilyl)oxy)methyl)morpholino)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (1.576 g, 2.251 mmol) in THF (11.26 ml) was added TBAF (3.38 ml, 3.38 mmol). The reaction mixture was stirred at room temperature 2.5 h. The reaction mixture was poured into a separatory funnel containing 1:1 saturated aqueous ammonium chloride and ethyl acetate. The aqueous layer was extracted with ethyl acetate (2×). The combined organics were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude solid was taken up in minimal dichloromethane and purified by column chromatography on the ISCO system (80 g, 0-50% EtOAc/CH2Cl2). (+/−)-2-((2-Chloro-5-cyano-3-(2-(hydroxymethyl)morpholino)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (0.926 g) was isolated as a yellow solid.

Workup

  1. additionThe reaction mixture was poured into a separatory funnel
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×)
  3. dry with materialThe combined organics were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. custompurified by column chromatography on the ISCO system (80 g, 0-50% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-1ba1f5ad9dbd482cac18fa42c98969bf
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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