1-(3-Aminopropyl)-2-pyrrolidinone → HCID 69480956, compound

HRID 2364404Notes

Reaction equation

HRID 2364404 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]1[C:23]2[C:18](=[N:19][CH:20]=[C:21]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[CH:22]=2)[C:17]([OH:32])=[C:16]([C:33](OCC)=[O:34])[C:15]1=[O:38].[NH2:39][CH2:40][CH2:41][CH2:42][N:43]1[CH2:47][CH2:46][CH2:45][C:44]1=[O:48].OS([O-])(=O)=O.[Na+]>CCO>[F:31][C:28]1[CH:27]=[CH:26][C:25]([CH2:24][C:21]2[CH:22]=[C:23]3[C:18]([C:17]([OH:32])=[C:16]([C:33]([NH:39][CH2:40][CH2:41][CH2:42][N:43]4[CH2:47][CH2:46][CH2:45][C:44]4=[O:48])=[O:34])[C:15](=[O:38])[N:14]3[CH2:13][CH2:12][NH:3][C:2]([C:10]3[C:5]([C:4]([NH:39][CH2:40][CH2:41][CH2:42][N:43]4[CH2:47][CH2:46][CH2:45][C:44]4=[O:48])=[O:11])=[CH:6][CH:7]=[CH:8][CH:9]=3)=[O:1])=[N:19][CH:20]=2)=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 821111-(3-Aminopropyl)-2-pyrrolidinoneHCID 516919Sodium BisulfateHCID 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

Product 1

HCID 69480956HCID 69480956, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of 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 (0.025 g, 0.049 mmol) in EtOH (1 mL) under nitrogen was treated with 1-(3-aminopropyl)-2-pyrrolidinone (0.0085 mL, 0.061 mmol) for 30 min. 150° C. The reaction was further microwaved for 30 min.@150° C. after the addition of an additional equivalent (0.0085 mL) of the amine, cooled to ambient temperature, and treated with 1N NaHSO4. The resulting suspension was filtered, washed with EtOH and the filtrate was concentrated in vacuo. The filtrate residue was purified by reversed phase HPLC. Pure fractions were combined and concentrated to afford the title compound as a pale yellow glass: 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.74 (ddd, J=12.42, 6.11, 5.90 Hz, 2 H), 1.84-1.95 (m, 2 H), 1.99-2.12 (m, 4 H), 2.41 (td, J=8.14, 2.25 Hz, 4 H), 3.21-3.32 (m, 2 H), 3.35-3.50 (m, 10 H), 3.61-3.73 (m, 2 H), 4.07 (s, 2 H), 4.48 (t, J=6.74 Hz, 2 H), 6.91-7.01 (m, 2 H), 7.17-7.23 (m, 2 H), 7.47-7.62 (m, 4 H), 7.71 (dd, J=5.26, 3.44 Hz, 1 H), 7.77 (t, J=5.90 Hz, 1 H), 8.18 (s, 1 H), 8.49 (s, 1 H), 10.31 (t, J=5.76 Hz, 1 H); ES+ MS: 754 (M+H+).

Workup

  1. custom150° C
  2. customThe reaction was further microwaved for 30 min.@150° C.
  3. filtrationThe resulting suspension was filtered
  4. washwashed with EtOH
  5. concentrationthe filtrate was concentrated in vacuo
  6. customThe filtrate residue was purified by reversed phase HPLC
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-d5b1cc4fe8904c8eacb444fb35187b03
Source dataset
uspto-grants-2014_04
Patent number
US08691991B2

Reaction notes

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