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

HRID 982720Notes

Reaction equation

HRID 982720 reaction equation
[Cl:1][C:2]1[CH:24]=[CH:23][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:11](=[O:22])[C:12]3[S:19][C:18]([CH2:20]Cl)=[CH:17][C:13]=3[N:14]([CH3:16])[CH:15]=2)=[O:9])=[CH:4][CH:3]=1.[OH:25][CH:26]([C:30]1[CH:35]=[CH:34][C:33]([NH:36][C:37](=[O:39])[CH3:38])=[CH:32][CH:31]=1)[CH2:27][NH:28][CH3:29].C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[C:37]([NH:36][C:33]1[CH:34]=[CH:35][C:30]([CH:26]([OH:25])[CH2:27][N:28]([CH2:20][C:18]2[S:19][C:12]3[C:11](=[O:22])[C:10]([C:8]([NH:7][CH2:6][C:5]4[CH:23]=[CH:24][C:2]([Cl:1])=[CH:3][CH:4]=4)=[O:9])=[CH:15][N:14]([CH3:16])[C:13]=3[CH:17]=2)[CH3:29])=[CH:31][CH:32]=1)(=[O:39])[CH3:38]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 10171338N-{4-[1-hydroxy-2-(methylamino)ethyl]phenyl}acetamideHCID 22563229N-(4-chlorobenzyl)-2-(chloromethyl)-4-methyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide

Product 1

HCID 104827542-{[{2-[4-(acetylamino)phenyl]-2-hydroxyethyl}(methyl)amino]methyl}-N-(4-chlorobenzyl)-4-methyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamideYield 58.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of N-(4-chlorobenzyl)-2-(chloromethyl)-4-methyl-7-oxo-4,7-dihydrothieno[3,2-b]pyridine-6-carboxamide (50 mg, 0.13 mmol), N-{4-[1-hydroxy-2-(methylamino)ethyl]phenyl}acetamide (42 mg, 0.20 mmol) and diisopropylethylamine (40 μL, 0.23 mmol) in dry DMF (2.7 mL) was heated to 60° C., becoming a solution. The reaction was stirred for 7 hours at that temperature. After cooling to room temperature, the solution was diluted with water (7 mL). The resulting milky suspension was stirred vigorously for 30 minutes, and then left standing overnight in the refrigerator. The mixture was filtered, and the collected solid was washed with water and dried in vacuo, leaving a white solid. Recrystallization from acetonitrile/water (dissolved with 3 mL of warming acetonitrile, cooled to room temperature, diluted with 2 mL of water, and then cooled to 0° C. overnight) gave the title compound (42 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 in the refrigerator
  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. dissolutiondissolved with 3 mL of warming acetonitrile
  11. temperaturecooled to room temperature
  12. additiondiluted with 2 mL of water
  13. temperaturecooled to 0° C. overnight)

Sources & evidence

ORD record
ord-368793a23f34438d9e6a5e138b6edb85
Source dataset
uspto-grants-2005_03
Patent number
US06861438B2

Reaction notes

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