Tetrabutylammonium Fluoride → (+/-)-2-(dimethylamino)ethyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamate

HRID 921652Notes

Reaction equation

HRID 921652 reaction equation
CCCC[N+](CCCC)(CCCC)CCCC.[F-].[Si]([O:26][C@H:27]1[C@H:32]([NH:33][C:34](=[O:41])[O:35][CH2:36][CH2:37][N:38]([CH3:40])[CH3:39])[CH2:31][CH2:30][N:29]([C:42]2[CH:47]=[C:46]([C:48]#[N:49])[CH:45]=[C:44]([NH:50][C:51]3[N:56]=[C:55]([NH:57][CH:58]4[CH2:60][CH2:59]4)[C:54]4=[N:61][CH:62]=[C:63]([C:64]#[N:65])[N:53]4[N:52]=3)[C:43]=2[Cl:66])[CH2:28]1)(C(C)(C)C)(C)C>C1COCC1>[Cl:66][C:43]1[C:44]([NH:50][C:51]2[N:56]=[C:55]([NH:57][CH:58]3[CH2:60][CH2:59]3)[C:54]3=[N:61][CH:62]=[C:63]([C:64]#[N:65])[N:53]3[N:52]=2)=[CH:45][C:46]([C:48]#[N:49])=[CH:47][C:42]=1[N:29]1[CH2:30][CH2:31][C@@H:32]([NH:33][C:34](=[O:41])[O:35][CH2:36][CH2:37][N:38]([CH3:39])[CH3:40])[C@H:27]([OH:26])[CH2:28]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 89922746(+/-)-2-(dimethylamino)ethyl ((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)carbamate

Product 1

HCID 89922892(+/-)-2-(dimethylamino)ethyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamateYield 77.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

TBAF (1M in THF, 0.059 mL, 0.059 mmol) was added to a solution of (+/−)-2-(dimethylamino)ethyl ((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)carbamate (34 mg, 0.049 mmol) in THF (1 mL) and the resulting solution was stirred at room temperature overnight. Solvent was evaporated and the residue was partitioned between dichloromethane and saturated sodium bicarbonate. The layers were separated and aqueous layer was extracted with dichloromethane/methanol (4/1) two more times. The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g gold column, eluting with 2-12% 2 N ammonia in methanol/dichloromethane). (+/−)-2-(dimethylamino)ethyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamate (22 mg) was obtained as a white solid.

Workup

  1. customSolvent was evaporated
  2. customthe residue was partitioned between dichloromethane and saturated sodium bicarbonate
  3. customThe layers were separated
  4. extractionaqueous layer was extracted with dichloromethane/methanol (4/1) two more times
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthe crude product was purified by flash chromatography on silica gel using
  9. washan automated ISCO system (24 g gold column, eluting with 2-12% 2 N ammonia in methanol/dichloromethane)

Sources & evidence

ORD record
ord-caf8c7c068624bd083d0d4bf9588226d
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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