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

HRID 23679Notes

Reaction equation

HRID 23679 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.[OH:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([CH:34]([OH:38])[CH2:35][NH:36][CH3:37])=[CH:30][CH:29]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[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[S:19][C:18]([CH2:20][N:36]([CH2:35][CH:34]([OH:38])[C:31]4[CH:32]=[CH:33][C:28]([CH2:27][OH:26])=[CH:29][CH:30]=4)[CH3:37])=[C:17]([CH3:22])[C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:24][CH:25]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 101712901-(4-(Hydroxymethyl)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 10174912N-(4-chlorobenzyl)-2-{[{2-hydroxy-2-[4-(hydroxymethyl)phenyl]ethyl}(methyl)amino]methyl}-3,4-dimethyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamideYield 68.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 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 (100 mg, 0.25 mmol), 1-[4-(hydroxymethyl)phenyl]-2-(methylamino)ethanol (Preparation 93) (69 mg, 0.38 mmol) and diisopropylethylamine (67 μL, 0.38 mmol) in dry DMF (5 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 water (15 mL). 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/DMF (15 mL/1 mL, dissolved with warming DMF, added with acetonitrile, and then cooled to 0° C. overnight) gave the title compound (92 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/DMF (15 mL/1 mL
  10. dissolutiondissolved with warming DMF
  11. additionadded with acetonitrile
  12. temperaturecooled to 0° C. overnight)

Sources & evidence

ORD record
ord-fc769c0f14ae478992cec63dd05e354d
Source dataset
uspto-grants-2005_02
Patent number
US06852731B2

Reaction notes

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