2-Bromoethanol → N-[(4-chlorophenyl)methyl]-7-(2-hydroxyethyl)-2-(3-hydroxyprop-1-ynyl)-4-oxo-thieno[2,3-b]pyridine-5-carboxamide

HRID 1978942Notes

Reaction equation

HRID 1978942 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[CH2:33][CH2:34][OH:35]>CN(C=O)C>[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]([CH2:33][CH2:34][OH:35])[CH:15]=2)=[O:9])=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 108982-BromoethanolHCID 11430Potassium CarbonateHCID 178522937HCID 178522937, compound

Product 1

HCID 6482391N-[(4-chlorophenyl)methyl]-7-(2-hydroxyethyl)-2-(3-hydroxyprop-1-ynyl)-4-oxo-thieno[2,3-b]pyridine-5-carboxamideYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °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) (0.250 g) in DMF (3 mL) is added K2CO3 (0.278 g) and 2-bromoethanol (0.14 mL). The reaction is heated to 100° C. and stirred for 18 h. The reaction mixture is concentrated in vacuo, and the resulting residue is partitioned between H2O (50 mL) and CH2Cl2 (50 mL). The aqueous layer is extracted with CH2Cl2 (3×50 mL). The combined organic layers are dried with MgSO4, filtered, and concentrated in vacuo to give a small amount of starting material. The desired product precipitates out of the aqueous layer as a tan solid. This material is recrystallized from methanol to yield 0.100 g (36%) of the title compound as a tan, crystalline solid.

Workup

  1. concentrationThe reaction mixture is concentrated in vacuo
  2. customthe resulting residue is partitioned between H2O (50 mL) and CH2Cl2 (50 mL)
  3. extractionThe aqueous layer is extracted with CH2Cl2 (3×50 mL)
  4. dry with materialThe combined organic layers are dried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a small amount of starting material
  8. customThe desired product precipitates out of the aqueous layer as a tan solid
  9. customThis material is recrystallized from methanol

Sources & evidence

ORD record
ord-f9c3d22ef0de4901b2a1db329afc21ac
Source dataset
uspto-grants-2001_05
Patent number
US06239142B1

Reaction notes

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