1,8-Diazabicyclo(5.4.0)undec-7-ene → ethyl 1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate

HRID 2364335Notes

Reaction equation

HRID 2364335 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][N:14]([C:34](=[O:41])[CH2:35][C:36]([O:38][CH2:39][CH3:40])=[O:37])[C:15]1[C:16]([C:29](OCC)=[O:30])=[N:17][CH:18]=[C:19]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH:20]=1.C1CCN2C(=NCCC2)CC1.OS([O-])(=O)=O.[Na+]>CCO.O>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH2:12][CH2:13][N:14]1[C:15]2[C:16](=[N:17][CH:18]=[C:19]([CH2:21][C:22]3[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=3)[CH:20]=2)[C:29]([OH:30])=[C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[C:34]1=[O:41]

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 516919Sodium BisulfateHCID 69482077ethyl 3-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl][3-(ethyloxy)-3-oxopropanoyl]amino}-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate

Product 1

HCID 69480967ethyl 1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-7-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A solution of ethyl 3-{[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl][3-(ethyloxy)-3-oxopropanoyl]amino}-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate (2.05 g, 3.65 mmol) in EtOH (75 mL) under nitrogen was treated with DBU (0.709 mL, 4.74 mmol). After stirring at ambient temperature for 15 min., the reaction mixture was treated with 1N NaHSO4 (5.0 mL). The resulting slurry was diluted with water, filtered, the filtered solid was washed with water, EtOH, and Et2O and thoroughly dried under high vacuum to provide the title compound as a white solid: 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.4 (t, J=7.0 Hz, 3 H), 4.0 (t, J=7.0 Hz, 4 H), 4.4 (t, J=6.5 Hz, 2 H), 4.5 (q, J=7.3 Hz, 2 H), 7.0 (t, J=8.5 Hz, 2 H), 7.1 (m, 2 H), 7.7 (dd, J=5.5, 3.1 Hz, 2 H), 7.8 (s, 1 H) 7.8 (m, 2 H), 8.4 (s, 1 H), 13.9 (none, 1 H); ES+ MS: 516 (M+H+).

Workup

  1. filtrationfiltered
  2. washthe filtered solid was washed with water, EtOH, and Et2O
  3. customthoroughly dried under high vacuum

Sources & evidence

ORD record
ord-82979fae7ce04578a55ba35f99883e98
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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