Tetrabutylammonium Fluoride → methyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamate

HRID 921702Notes

Reaction equation

HRID 921702 reaction equation
[Si]([O:8][C@H:9]1[C@H:14]([NH:15][C:16](=[O:19])[O:17][CH3:18])[CH2:13][CH2:12][N:11]([C:20]2[CH:25]=[C:24]([C:26]#[N:27])[CH:23]=[C:22]([NH:28][C:29]3[N:34]=[C:33]([N:35](CC)[CH2:36][C:37]4C=CC(OC)=CC=4)[C:32]4=[N:47][CH:48]=[C:49]([C:50]#[N:51])[N:31]4[N:30]=3)[C:21]=2[Cl:52])[CH2:10]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>O1CCCC1>[Cl:52][C:21]1[C:22]([NH:28][C:29]2[N:34]=[C:33]([NH:35][CH2:36][CH3:37])[C:32]3=[N:47][CH:48]=[C:49]([C:50]#[N:51])[N:31]3[N:30]=2)=[CH:23][C:24]([C:26]#[N:27])=[CH:25][C:20]=1[N:11]1[CH2:12][CH2:13][C@@H:14]([NH:15][C:16](=[O:19])[O:17][CH3:18])[C@H:9]([OH:8])[CH2:10]1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 131732392methyl ((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-m ethoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)carbamate

Product 1

HCID 89932121methyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamateYield 133.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

methyl ((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)carbamate (140 mg, 0.188 mmol) was dissolved into tetrahydrofuran (2 mL). TBAF 1M in THF (0.244 mL, 0.244 mmol) was added. The mixture was stirred at room temperature overnight. The mixture was concentrated to dryness, then diluted with EtOAc (50 ml) and washed with sat. NaHCO3. The water layer was extracted with 20 ml EtOAc. The combined organic layer was washed with brine, dried over MgSO4, filtered and concentrated to dryness to give 128 mg of product, which was used further without purification.

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. additiondiluted with EtOAc (50 ml)
  3. washwashed with sat. NaHCO3
  4. extractionThe water layer was extracted with 20 ml EtOAc
  5. washThe combined organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-2f5d012eb9a84175a0d29d63cefe0fea
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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