Water → N-(4-Chlorobenzyl)-2-(((3R)-3-hydroxypyrrolidin-1-yl)methyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamide

HRID 1814869Notes

Reaction equation

HRID 1814869 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.[OH:34][C@@H:35]1[CH2:39][CH2:38][NH:37][CH2:36]1.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:37]4[CH2:38][CH2:39][C@@H:35]([OH:34])[CH2:36]4)[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 2759337(R)-3-PyrrolidinolHCID 10126210N-(4-Chlorobenzyl)-2-(chloromethyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamide

Product 1

HCID 10309940N-(4-Chlorobenzyl)-2-(((3R)-3-hydroxypyrrolidin-1-yl)methyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

N,N-Diisopropylethylamine (0.48 mL) and N-(4-chlorobenzyl)-2-(chloromethyl)-7-methyl-4-oxo-4,7-dihydrofuro[2,3-b]pyridine-5-carboxamide (Example 2, 0.500 g) were added to a solution of (R)-3-hydroxypyrrolidine (0.22 mL) in DMF (30 mL). The reaction mixture was heated to 90° C. for 2 h. The mixture was allowed to cool to room temperature, poured into water (60 mL), and extracted with ethyl acetate (4×50 mL) then CH2Cl2 (2×50 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, 95/5) followed by recrystallization from ethyl acetate to yield 0.360 g of the title compound as a pale yellow solid. Physical characteristics. M.p. 189-190° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.64, 8.54, 7.41-7.32, 6.85, 4.73, 4.55, 4.22-4.16, 3.93, 3.68, 2.78-2.74, 2.68-2.62, 2.52-2.47, 2.41-2.37, 2.02-1:94, 1.58-1.50; MS (ESI+) m/z 416 (M+H)+; [α]25D=−3 (CH2Cl2).

Workup

  1. temperatureto cool to room temperature
  2. extractionextracted with ethyl acetate (4×50 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, 95/5)
  7. customfollowed by recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-d46ebad4a25b45d8be2d0118ae42b937
Source dataset
uspto-grants-2005_04
Patent number
US06878705B2

Reaction notes

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