Potassium Carbonate → (4R,5S)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-2-(2-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxohexanoate

HRID 1056232Notes

Reaction equation

HRID 1056232 reaction equation
C1(NC2C(C)=NC3C(N=2)=C(C2NC4[C@H]([C@H](O)C)NC(=O)C=4C=2)C(F)=CC=3)CC1.Br[CH2:30][C:31]([C:33]1[C:42]([F:43])=[CH:41][CH:40]=[C:39]2[C:34]=1[N:35]=[C:36]([NH:45][CH:46]1[CH2:48][CH2:47]1)[C:37]([CH3:44])=[N:38]2)=[O:32].[C:49]([O:53][C:54]([NH:56][C@H:57]([C@@H:66]([O:68][Si:69]([C:72]([CH3:75])([CH3:74])[CH3:73])([CH3:71])[CH3:70])[CH3:67])[C:58](=[O:65])[CH2:59][C:60]([O:62][CH2:63][CH3:64])=[O:61])=[O:55])([CH3:52])([CH3:51])[CH3:50].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCO.CC(O)=O>[C:49]([O:53][C:54]([NH:56][C@H:57]([C@@H:66]([O:68][Si:69]([C:72]([CH3:74])([CH3:73])[CH3:75])([CH3:70])[CH3:71])[CH3:67])[C:58](=[O:65])[CH:59]([CH2:30][C:31]([C:33]1[C:42]([F:43])=[CH:41][CH:40]=[C:39]2[C:34]=1[N:35]=[C:36]([NH:45][CH:46]1[CH2:48][CH2:47]1)[C:37]([CH3:44])=[N:38]2)=[O:32])[C:60]([O:62][CH2:63][CH3:64])=[O:61])=[O:55])([CH3:52])([CH3:50])[CH3:51]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 897821632-Bromo-1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanoneHCID 89783316(6R)-2-(3-(cyclopropylamino)-6-fluoro-2-methyl-5-quinoxalinyl)-6-((1R)-1-hydroxyethyl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-oneHCID 131736417(4R,5S)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-3-oxohexanoate

Product 1

HCID 131736423(4R,5S)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-2-(2-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxohexanoateYield 96%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

This compound (2.43 g, 73% yield) as a bright yellow crystalline solid was prepared according to the procedures described for Intermediate 352b, using 2-bromo-1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone (613) (1.82 g, 5.39 mmol) and (4R,5S)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-3-oxohexanoate (615) (2.61 g, 6.47 mmol) and K2CO3 (0.931 g, 6.73 mmol) in DMF (10 mL) as the strafing materials, followed by subsequent treatment of the resulting (4R,5S)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-2-(2-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxohexanoate (353a) (3.42 g, 96% yield, LC-MS m/z 661.1, [M+H]+) with NH4OAc (5.98 g, 78 mmol) in 10 mL of EtOH and 5 mL of AcOH. 19F NMR (DMSO-d6; 376 MHz): δ −110.91 (s, 1F). LC-MS m/z 642.2, [M+H]+.

Sources & evidence

ORD record
ord-f2da4075e4364282b0540ce0fd849277
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

Loading…