Potassium Carbonate → N-(4-Chlorobenzyl)-7-[2-(diethylamino)ethyl]-2-(3-hydroxy-1-propynyl)-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamide hydrochloride

HRID 1978943Notes

Reaction equation

HRID 1978943 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11]([OH:23])=[C:12]3[CH:18]=[C:17]([C:19]#[C:20][CH2:21][OH:22])[S:16][C:13]3=[N:14][CH:15]=2)=[O:9])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].Br.Br[CH2:34][CH2:35][N:36]([CH2:39][CH3:40])[CH2:37][CH3:38].Br.BrCCNCC>CN(C=O)C.O>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:23])[C:12]3[CH:18]=[C:17]([C:19]#[C:20][CH2:21][OH:22])[S:16][C:13]=3[N:14]([CH2:34][CH2:35][N:36]([CH2:39][CH3:40])[CH2:37][CH3:38])[CH:15]=2)=[O:9])=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 11430Potassium Carbonate3×HCID 706072-Bromoethyldiethylammonium bromideHCID 13183153(2-Bromoethyl)(ethyl)amine hydrobromideHCID 178522937HCID 178522937, compound

Product 1

HCID 18380166N-(4-Chlorobenzyl)-7-[2-(diethylamino)ethyl]-2-(3-hydroxy-1-propynyl)-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxamide hydrochlorideYield 20%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of N-(4-chlorobenzyl)-4-hydroxy-2-(3-hydroxy-1-propynyl)thieno[2,3-b]pyridine-5-carboxamide (Example No. 5) (0.300 g) in DMF (4 mL) is added K2CO3 (0.334 g) and 2-bromo-N,N-diethylethylamine hydrobromide (0.420 g). The reaction is heated to 90° C. After 4.5 h, an additional 0.111 g of K2CO3 is added and the reaction is stirred at 90° C. for 3 d. An additional 0.210 g of 2-bromo-N,N-diethylamine hydrobromide and 0.111 g of K2CO3 are added and the reaction is stirred for an additional 5 h. The reaction mixture is added to H2O and then concentrated in vacuo. The resulting brown solid is purified via column chromatography (CH2Cl2:CH3OH; 98:2, 95:5). The resulting yellow solid is dissolved in methanolic HCl and concentrated in vacuo. The salt is recrystallized twice from ethanol to yield 0.080 g (20%) of the title compound as a pale yellow solid.

Workup

  1. stirringthe reaction is stirred for an additional 5 h
  2. concentrationconcentrated in vacuo
  3. customThe resulting brown solid is purified via column chromatography (CH2Cl2:CH3OH; 98:2, 95:5)
  4. dissolutionThe resulting yellow solid is dissolved in methanolic HCl
  5. concentrationconcentrated in vacuo
  6. customThe salt is recrystallized twice from ethanol

Sources & evidence

ORD record
ord-20b8379d59294339ad9c662d5c10a746
Source dataset
uspto-grants-2001_05
Patent number
US06239142B1

Reaction notes

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