Cyclopropylamine → N-Cyclopropyl-7-(4-fluorobenzyl)-4-hydroxy-2-oxo-1-[2-(2-oxopyrrolidin-1-yl)ethyl]-1,2-dihydro-1,5-naphthyridine-3-carboxamide

HRID 2364142Notes

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]([O:28]CC)=O)[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.[CH:34]1([NH2:37])[CH2:36][CH2:35]1>CCO>[CH:34]1([NH:37][C:26]([C:12]2[C:13](=[O:25])[N:14]([CH2:17][CH2:18][N:19]3[CH2:23][CH2:22][CH2:21][C:20]3=[O:24])[C:15]3[C:10]([C:11]=2[OH:31])=[N:9][CH:8]=[C:7]([CH2:6][C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:33][CH:32]=2)[CH:16]=3)=[O:28])[CH2:36][CH2:35]1

Participants

Conditions

Temperature: 120 °C

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 (47 mg, 104 μmol) and cyclopropylamine (0.1 mL, 1.44 mmol) in EtOH (3 mL) was heated at 120° C. in a microwave for 20 min. The mixture was concentrated in vacuo, triturated with EtOH and the product was collected by filtration as a white solid: 1H NMR (CDCl3) δ 10.06 (1H, d, J=3 Hz), 8.57 (1H, d, J=1.2 Hz), 8.08 (1H, s), 7.25 (2H, dd, J=8.5, 5.5 Hz), 7.00 (2H, t, J=8.5 Hz), 4.32 (2H, q, J=7 Hz), 4.14 (2H, s), 3.49 (2H, t, J=7.4 Hz), 3.41 (2H, t, J=7 Hz), 2.95 (1H, m), 2.32 (2H, t, J=8 Hz), 1.97 (2H, m), 0.90 (2H, m), 0.69 (2H, m); HRMS calcd for C25H25FN4O4+H+: 465.1938. Found: 465.1932.

Workup

concentrationThe mixture was concentrated in vacuo
customtriturated with EtOH
filtrationthe product was collected by filtration as a white solid

Sources & evidence

ORD record: ord-791e86d5586b41cba0e318351a91055f
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08691991B2

Reaction notes

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