Tetrabutylammonium Fluoride → 2-chloro-N-((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)acetamide

HRID 1430861Notes

Reaction equation

HRID 1430861 reaction equation
[Si]([O:8][C@H:9]1[C@H:14]([NH:15][C:16](=[O:19])[CH2:17][Cl: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]([CH:45]4[CH2:47][CH2:46]4)[CH2:36][C:37]4[CH:42]=[CH:41][C:40]([O:43][CH3:44])=[CH:39][CH:38]=4)[C:32]4=[N:48][CH:49]=[C:50]([C:51]#[N:52])[N:31]4[N:30]=3)[C:21]=2[Cl:53])[CH2:10]1)(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:18][CH2:17][C:16]([NH:15][C@@H:14]1[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]([CH:45]4[CH2:47][CH2:46]4)[CH2:36][C:37]4[CH:38]=[CH:39][C:40]([O:43][CH3:44])=[CH:41][CH:42]=4)[C:32]4=[N:48][CH:49]=[C:50]([C:51]#[N:52])[N:31]4[N:30]=3)[C:21]=2[Cl:53])[CH2:10][C@H:9]1[OH:8])=[O:19]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 86708552HCID 86708552, compound

Product 1

HCID 867085532-chloro-N-((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)acetamideYield 60.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To (+/−)-N-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)-2-chloroacetamide (43 mg, 0.055 mmol) in THF (1 mL) was added TBAF (1M in THF, 0.112 mL, 0.112 mmol) and the reaction solution was stirred at room temperature overnight. LCMS showed completion of reaction. Solvent was evaporated and the crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 0.5-4% methanol/dichloromethane) to give (+/−)-2-chloro-N-((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)acetamide (22 mg) as a white solid.

Workup

  1. customcompletion of reaction
  2. customSolvent was evaporated
  3. customthe crude product was purified by flash chromatography on silica gel using
  4. washan automated ISCO system (24 g column, eluting with 0.5-4% methanol/dichloromethane)

Sources & evidence

ORD record
ord-e5eddba66cbd44749711610f20664dd4
Source dataset
uspto-grants-2015_01
Patent number
US08940736B2

Reaction notes

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