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

HRID 1847074Notes

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][CH2:14][C@@H:15]3[CH2:17][O:16]3)[C:7]=2[N:18]=1.[NH2:19][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:16][C@H:15]([CH2:14][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:18][C:7]1=2)[CH2:17][NH: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: 80 °C

Procedure

In a mixed solvent (16 ml) of ethanol-water (9:1) were suspended 6-methoxy-4-{2-[(2R)-oxiran-2-yl]ethyl}pyrido[2,3-b]pyrazin-3(4H)-one (Reference Example 77; 400 mg, 1.62 mmol) and 6-[(4S)-4-amino-2-oxopyrrolidin-1-yl]-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (Reference Example 22; 402 mg, 1.62 mmol), and the suspension was stirred in a sealed tube at 80° C. for 16 hours. The solvent was removed from the reaction solution under reduced pressure and the obtained residue was purified by silica gel column chromatography (chloroform/methanol) to yield 288 mg (36%) of the title compound in the form of a yellowish solid.

Workup

customThe solvent was removed from the reaction solution under reduced pressure
customthe obtained residue was purified by silica gel column chromatography (chloroform/methanol)

Sources & evidence

ORD record: ord-bfaebbc3426540d58f93b232e63a08d8
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952010B2

Reaction notes

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