Water → N-(4-Chlorobenzyl)-2-(((2-hydroxy-2-(5-phenyl-2-furyl)ethyl)(methyl)amino)methyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamide

HRID 1814882Notes

Reaction equation

HRID 1814882 reaction equation
C(N(CC)C(C)C)(C)C.[Cl:10][C:11]1[CH:33]=[CH:32][C:14]([CH2:15][NH:16][C:17]([C:19]2[C:20](=[O:31])[C:21]3[CH:28]=[C:27]([CH2:29]Cl)[O:26][C:22]=3[N:23]([CH3:25])[CH:24]=2)=[O:18])=[CH:13][CH:12]=1.[CH3:34][NH:35][CH2:36][CH:37]([C:39]1[O:40][C:41]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[CH:42][CH:43]=1)[OH:38].O>CN(C=O)C>[Cl:10][C:11]1[CH:33]=[CH:32][C:14]([CH2:15][NH:16][C:17]([C:19]2[C:20](=[O:31])[C:21]3[CH:28]=[C:27]([CH2:29][N:35]([CH2:36][CH:37]([OH:38])[C:39]4[O:40][C:41]([C:44]5[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=5)=[CH:42][CH:43]=4)[CH3:34])[O:26][C:22]=3[N:23]([CH3:25])[CH:24]=2)=[O:18])=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 10126210N-(4-Chlorobenzyl)-2-(chloromethyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamideHCID 10192672HCID 10192672, compound

Product 1

HCID 10218306N-(4-Chlorobenzyl)-2-(((2-hydroxy-2-(5-phenyl-2-furyl)ethyl)(methyl)amino)methyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamideYield 80.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

N,N-Diisopropylethylamine (0.17 mL) was added to a solution of N-(4-chlorobenzyl)-2-(chloromethyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamide (Example 2, 0.183 g) and rac-2-(methylamino)-1-(5-phenyl-2-furyl)ethanol (Preparation 55, 0.217 g) in DMF (15 mL). The reaction mixture was heated to 90° C. for 2 h. The mixture was allowed to cool to room temperature, poured into water (50 mL), and was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine (50 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified by column chromatography (CH2Cl2/methanol, 100/1; 50/1; 25/1) and crystallized from ethyl acetate/CH2Cl2/diethyl ether to afford 0.22 g of the title compound as a white solid. Physical characteristics. M.p. 115-119°C.; 1H NMR (400 MHz, DMSO-d6) δ 10.63, 8.40, 7.56, 7.42-7.30, 7.17, 6.89, 6.84, 6.37, 5.34, 4.74, 4.54, 3.80, 3.74, 3.67, 2.88, 2.68, 2.33; MS (ESI+) m/z 546 (M+H)+.

Workup

  1. temperatureto cool to room temperature
  2. extractionwas extracted with ethyl acetate (3×100 mL)
  3. washThe combined organic layers were washed with brine (50 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (CH2Cl2/methanol, 100/1; 50/1; 25/1)
  8. customcrystallized from ethyl acetate/CH2Cl2/diethyl ether

Sources & evidence

ORD record
ord-1fa8a6d0778f47949f915474333cc7b2
Source dataset
uspto-grants-2005_04
Patent number
US06878705B2

Reaction notes

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