Cesium carbonate → 2-((2-Chloro-5-cyano-3-(4-(2-hydroxyethyl)-2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

HRID 921885Notes

Reaction equation

HRID 921885 reaction equation
[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][C:9]2=[O:14])=[CH:6][C:5]([C:15]#[N:16])=[CH:4][C:3]=1[NH:17][C:18]1[N:23]=[C:22]([N:24]([CH:34]2[CH2:36][CH2:35]2)CC2C=CC(OC)=CC=2)[C:21]2=[N:37][CH:38]=[C:39]([C:40]#[N:41])[N:20]2[N:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:49][CH2:50][O:51][Si](C(C)(C)C)(C)C>CN(C=O)C>[Cl:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][N:11]([CH2:49][CH2:50][OH:51])[CH2:10][C:9]2=[O:14])=[CH:6][C:5]([C:15]#[N:16])=[CH:4][C:3]=1[NH:17][C:18]1[N:23]=[C:22]([NH:24][CH:34]2[CH2:35][CH2:36]2)[C:21]2=[N:37][CH:38]=[C:39]([C:40]#[N:41])[N:20]2[N:19]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 3608067(2-Bromoethoxy)-tert-butyldimethylsilaneHCID 899226992-((2-Chloro-5-cyano-3-(2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Product 1

HCID 899231242-((2-Chloro-5-cyano-3-(4-(2-hydroxyethyl)-2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-((2-chloro-5-cyano-3-(2-oxopiperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (10 mg, 0.018 mmol) in DMF (0.5 mL) was added cesium carbonate (25 mg, 0.077 mmol) followed by (2-bromoethoxy)(tert-butyl)dimethylsilane (8 mg, 0.033 mmol). The reaction mixture was stirred at room temperature overnight. LC-MS indicated desired product. It was then filtered through a pad of Celite, rinsed with EtOAc. The crude was dissolved in DCE (1 mL), anisole (7.68 μl, 0.070 mmol) (one drop) was added followed by TFA (0.5 mL, 6.49 mmol). The resulting reaction mixture was heated at 60° C. for 1 h. LC-MS indicated completion, and then it was cooled and concentrated. The crude was dissolved in methanol and neutralized with 7N ammonia in methanol. After stirring for 10 min it was concentrated, purification via preparative HPLC gave the title compound as a yellow solid (3.4 mg).

Sources & evidence

ORD record
ord-4fb30ead96b247858eb926acaa4b0cfd
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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