2-Methoxyethylamine → 7-(4-Fluorobenzyl)-4-hydroxy-N-(2-methoxyethyl)-2-oxo-1-[2-(2-oxopyrrolidin-1-yl)ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxamide

HRID 2364430Notes

Reaction equation

HRID 2364430 reaction equation
[F:1][C:2]1[CH:33]=[CH:32][C:5]([CH2:6][C:7]2[CH:16]=[C:15]3[C:10]([C:11]([OH:31])=[C:12]([C:26](OCC)=[O:27])[C:13](=[O:25])[N:14]3[CH2:17][CH2:18][N:19]3[CH2:23][CH2:22][CH2:21][C:20]3=[O:24])=[N:9][CH:8]=2)=[CH:4][CH:3]=1.[CH3:34][O:35][CH2:36][CH2:37][NH2:38]>C(O)(C)C>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][C:7]2[CH:16]=[C:15]3[C:10]([C:11]([OH:31])=[C:12]([C:26]([NH:38][CH2:37][CH2:36][O:35][CH3:34])=[O:27])[C:13](=[O:25])[N:14]3[CH2:17][CH2:18][N:19]3[CH2:23][CH2:22][CH2:21][C:20]3=[O:24])=[N:9][CH:8]=2)=[CH:32][CH:33]=1

Participants

4

Reactant 2

HCID 80182-MethoxyethylamineHCID 58882907Ethyl 7-(4-fluorobenzyl)-4-hydroxy-2-oxo-1-[2-oxopyrrolidin-1-yl ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxylate

Product 1

HCID 546955957-(4-Fluorobenzyl)-4-hydroxy-N-(2-methoxyethyl)-2-oxo-1-[2-(2-oxopyrrolidin-1-yl)ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxamide

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Procedure

A mixture of ethyl 7-(4-fluorobenzyl)-4-hydroxy-2-oxo-1-[2-(2-oxopyrrolidin-1-yl)ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxylate (1.13 g, 2.50 mmol) and 2-methoxyethylamine (1.1 mL, 12.5 mmol) in isopropanol (20 mL) was heated at reflux for 3 hrs. After cooling, the resulting slurry was diluted with isopropanol (10 mL) and filtered. The precipitate was partitioned between CH2Cl2 and 1N NaHSO4. After separating the layers, the aqueous phase was back-extracted with CH2Cl2 and the combined organics were dried over Na2SO4, filtered and evaporated in vacuo to provide the product as a white solid. The isopropanol was evaporated in vacuo and the residue was partitioned between CH2Cl2 and 1N NaHSO4. After separating the layers, the aqueous phase was back-extracted with CH2Cl2 and the combined organics were dried over Na2SO4, filtered and evaporated in vacuo to provide an additional crop of the product as a white solid: 1H NMR (CDCl3) δ 10.27 (1H, br m), 8.55 (1H, s), 8.06 (1H, s), 7.24 (2H, m), 6.99 (2H, t, J=8.6 Hz), 4.35 (2H, t, J=7 Hz), 4.14 (2H, s), 3.65 (2H, m), 3.59 (2H, m), 3.50 (2H, t, J=7 Hz), 3.44 (2H, m), 3.42 (3H, s), 2.31 (2H, t, J=8 Hz), 1.97 (2H, m); ES+ MS: 483 (M+H+).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 3 hrs
  3. temperatureAfter cooling
  4. filtrationfiltered
  5. customThe precipitate was partitioned between CH2Cl2 and 1N NaHSO4
  6. customAfter separating the layers
  7. extractionthe aqueous phase was back-extracted with CH2Cl2
  8. dry with materialthe combined organics were dried over Na2SO4
  9. filtrationfiltered
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-d13ae1a8d7164c2aabf8e322e1d45417
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

Loading…