Ethyl Acetate → HCID 86708483, compound

HRID 921629Notes

Reaction equation

HRID 921629 reaction equation
[Si]([O:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]2[C:16]([Cl:48])=[C:17]([NH:23][C:24]3[N:29]=[C:28]([N:30]([CH:40]4[CH2:42][CH2:41]4)[CH2:31][C:32]4[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=4)[C:27]4=[N:43][CH:44]=[C:45]([C:46]#[N:47])[N:26]4[N:25]=3)[CH:18]=[C:19]([C:21]#[N:22])[CH:20]=2)[CH2:11][CH2:10]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C(=O)(O)[O-].[Na+].C(OCC)(=O)C>O1CCCC1>[Cl:48][C:16]1[C:15]([N:12]2[CH2:11][CH2:10][CH:9]([OH:8])[CH2:14][CH2:13]2)=[CH:20][C:19]([C:21]#[N:22])=[CH:18][C:17]=1[NH:23][C:24]1[N:29]=[C:28]([N:30]([CH:40]2[CH2:42][CH2:41]2)[CH2:31][C:32]2[CH:33]=[CH:34][C:35]([O:38][CH3:39])=[CH:36][CH:37]=2)[C:27]2=[N:43][CH:44]=[C:45]([C:46]#[N:47])[N:26]2[N:25]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 867084842-((3-(4-((Tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Product 1

HCID 86708483HCID 86708483, compoundYield 67.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

(I13D): To a round bottom flask charged with 2-((3-(4-((tert-butyldimethylsilyl)oxy)piperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (I13C) (1.446 g, 2.113 mmol) in tetrahydrofuran (21.13 ml) and cooled to 0° C. was added TBAF (4.23 ml, 4.23 mmol). The reaction mixture was stirred at room temperature 2 d. The reaction mixture was poured into a separatory funnel containing saturated aqueous sodium bicarbonate and ethyl acetate. The aqueous layer was extracted with ethyl acetate (3×). The combined organics were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude residue was taken up in dichloromethane. A white precipitate was isolated by filtration. The filtrate was purified by column chromatography on the ISCO system (40 g, 0-50% EtOAc/CH2Cl2). The precipitate was combined with the column isolate to provide 2-((2-chloro-5-cyano-3-(4-hydroxypiperidin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (0.816 g) as a white solid.

Workup

  1. additionThe reaction mixture was poured into a separatory funnel
  2. extractionThe aqueous layer was extracted with ethyl acetate (3×)
  3. washThe combined organics were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customA white precipitate was isolated by filtration
  8. customThe filtrate was purified by column chromatography on the ISCO system (40 g, 0-50% EtOAc/CH2Cl2)
  9. customisolate

Sources & evidence

ORD record
ord-835ffd85f2724553806e416965c9257c
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

Loading…