Diisopropylethylamine → N-(4-chlorobenzyl)-2-{[(2-hydroxy-2-{3-[2-(2-methoxyethoxy)ethoxy]phenyl}ethyl)(methyl)amino]methyl}-3,4-dimethyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide

HRID 23661Notes

Reaction equation

HRID 23661 reaction equation
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:23])[C:12]3[S:19][C:18]([CH2:20]Cl)=[C:17]([CH3:22])[C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1.[CH3:26][O:27][CH2:28][CH2:29][O:30][CH2:31][CH2:32][O:33][C:34]1[CH:35]=[C:36]([CH:40]([OH:44])[CH2:41][NH:42][CH3:43])[CH:37]=[CH:38][CH:39]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:23])[C:12]3[S:19][C:18]([CH2:20][N:42]([CH2:41][CH:40]([OH:44])[C:36]4[CH:37]=[CH:38][CH:39]=[C:34]([O:33][CH2:32][CH2:31][O:30][CH2:29][CH2:28][O:27][CH3:26])[CH:35]=4)[CH3:43])=[C:17]([CH3:22])[C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 102146891-{3-[2-(2-Methoxyethoxy)ethoxy]phenyl}-2-(methylamino)ethanolHCID 22574363N-(4-chlorobenzyl)-2-(chloromethyl)-3,4-dimethyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide

Product 1

HCID 22574412N-(4-chlorobenzyl)-2-{[(2-hydroxy-2-{3-[2-(2-methoxyethoxy)ethoxy]phenyl}ethyl)(methyl)amino]methyl}-3,4-dimethyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamideYield 81.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of N-(4-chlorobenzyl)-2-(chloromethyl)-3,4-dimethyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide (85 mg, 0.21 mmol), 1-{3-[2-(2-methoxyethoxy)ethoxy]phenyl}-2-(methylamino)ethanol (Preparation 44) (85 mg, 0.32 mmol) and diisopropylethylamine (56 μL, 0.32 mmol) in dry DMF (4.4 mL) was heated to 60° C., becoming a solution. The reaction was stirred for 5 hours at that temperature. After cooling to room temperature, the solution was diluted with ice (6 g). The resulting milky suspension was stirred vigorously for 30 minutes, and then left standing overnight at room temp. The mixture was filtered, and the collected solid was washed with water and dried in vacuo, leaving a white solid. Recrystallization from acetonitrile/water (10 mL, 1:1, v/v, dissolved with warming acetonitrile, diluted with water and then cooled to 0° C. overnight) gave the title compound (107 mg) as a white solid.

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringThe resulting milky suspension was stirred vigorously for 30 minutes
  3. waitleft
  4. waitstanding overnight at room temp
  5. filtrationThe mixture was filtered
  6. washthe collected solid was washed with water
  7. customdried in vacuo
  8. customleaving a white solid
  9. customRecrystallization from acetonitrile/water (10 mL, 1:1, v/v
  10. dissolutiondissolved with warming acetonitrile
  11. additiondiluted with water
  12. temperaturecooled to 0° C. overnight)

Sources & evidence

ORD record
ord-d3744b61b4c9472cb57a90723bdd9466
Source dataset
uspto-grants-2005_02
Patent number
US06852731B2

Reaction notes

Loading…