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

HRID 1814874Notes

Reaction equation

HRID 1814874 reaction equation
C(N(CC)C(C)C)(C)C.[CH3:10][NH:11][CH2:12][CH:13]([C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)[OH:14].[Cl:21][C:22]1[CH:44]=[CH:43][C:25]([CH2:26][NH:27][C:28]([C:30]2[C:31](=[O:42])[C:32]3[CH:39]=[C:38]([CH2:40]Cl)[O:37][C:33]=3[N:34]([CH3:36])[CH:35]=2)=[O:29])=[CH:24][CH:23]=1.O>CN(C=O)C>[Cl:21][C:22]1[CH:44]=[CH:43][C:25]([CH2:26][NH:27][C:28]([C:30]2[C:31](=[O:42])[C:32]3[CH:39]=[C:38]([CH2:40][N:11]([CH2:12][CH:13]([OH:14])[C:15]4[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=4)[CH3:10])[O:37][C:33]=3[N:34]([CH3:36])[CH:35]=2)=[O:29])=[CH:24][CH:23]=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 224987342-(Methylamino)-1-(pyridin-3-yl)ethan-1-ol

Product 1

HCID 10128013N-(4-Chlorobenzyl)-2-(((2-hydroxy-2-pyridin-3-ylethyl)(methyl)amino)methyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamideYield 37.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

N,N-Diisopropylethylamine (0.11 mL) and 2-(methylamino)-1-pyridin-3-ylethanol (Preparation 39, 0.094 g) were added to a suspension of N-(4-chlorobenzyl)-2-(chloromethyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamide (Example 2, 0.150 g) in DMF (10 mL). The reaction mixture was heated to 90° C. for 1 h. The mixture was allowed to cool to room temperature, poured into water (25 mL), and was extracted with CH2Cl2 (4×25 mL). The combined organic layers were dried (MgSO4), filtered, and concentrated in vacuo. The resulting solid was purified by column chromatography (CH2Cl2/methanol; 98/2, 97/3, 96/4, 95/5) followed by recrystallization from ethyl acetate to yield 0.074 g of the title compound as a pale yellow solid. Physical characteristics. M.p. 145-149° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.64, 8.54, 8.50, 8.40-8.39, 7.69-7.67, 7.41-7.33, 7.29-7.25, 6.83, 5.33, 4.77-4.73, 4.55, 3.88, 3.71, 2.67-2.55, 2.32; MS (ESI+) m/z 481 (M+H)+.

Workup

  1. temperatureto cool to room temperature
  2. extractionwas extracted with CH2Cl2 (4×25 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting solid was purified by column chromatography (CH2Cl2/methanol; 98/2, 97/3, 96/4, 95/5)
  7. customfollowed by recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-ab081c68887548339a30f11c24d61719
Source dataset
uspto-grants-2005_04
Patent number
US06878705B2

Reaction notes

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