6-[(4R)-4-(Aminomethyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one → 6-[(4R)-4-({[(2S)-2-Hydroxy-3-(6-methoxy-3-oxopyrido[2,3-b]pyrazin-4(3H)-yl)propyl]amino}methyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one

HRID 1847061Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:11]=[CH:10][C:9](=[O:12])[N:8]([CH2:13][C@@H:14]3[CH2:16][O:15]3)[C:7]=2[N:17]=1.[NH2:18][CH2:19][C@@H:20]1[CH2:24][N:23]([C:25]2[CH:26]=[CH:27][C:28]3[O:29][CH2:30][C:31](=[O:35])[NH:32][C:33]=3[N:34]=2)[C:22](=[O:36])[CH2:21]1>C(O)C.O>[OH:15][C@H:14]([CH2:13][N:8]1[C:9](=[O:12])[CH:10]=[N:11][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[N:17][C:7]1=2)[CH2:16][NH:18][CH2:19][C@@H:20]1[CH2:24][N:23]([C:25]2[CH:26]=[CH:27][C:28]3[O:29][CH2:30][C:31](=[O:35])[NH:32][C:33]=3[N:34]=2)[C:22](=[O:36])[CH2:21]1

Participants

Conditions

Temperature: 60 °C

Procedure

In a mixed solvent (60 ml) of ethanol and water (9:1) were dissolved 6-methoxy-4-[(2R)-oxiran-2-ylmethyl]pyrido[2,3-b]pyrazin-3(4H)-one (2.94 g, 12.60 mmol) and 6-[(4R)-4-(aminomethyl)-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Reference Example 54; 3.30 g, 12.60 mmol), and the obtained mixture was then stirred in a sealed tube at 60° C. for 15 hours. Thereafter, the reaction solution was cooled in the air, and the solvent was then removed under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol) to yield 1.73 g (28%) of the above-captioned compound in the form of a light yellow solid.

Workup

temperatureThereafter, the reaction solution was cooled in the air
customthe solvent was then removed under reduced pressure
customThe residue was purified by silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record: ord-871518cdf5b44747ae9ad01e54e63e2c
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952010B2

Reaction notes

Loading…