HCID 21091408, compound → (-)-n-((6r,7s)-6-Cyclopropyl-2-fluoro-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)-2-hydroxy-2-methyl-n'-(2,2,3,3,3-pentafluoro-propyl)-malonamide

HRID 1348637Notes

Reaction equation

HRID 1348637 reaction equation
[OH:1][C:2]([CH3:17])([C:6]([NH:8][CH2:9][C:10]([F:16])([F:15])[C:11]([F:14])([F:13])[F:12])=[O:7])[C:3]([OH:5])=O.[NH2:18][C@@H:19]1[C:25](=[O:26])[NH:24][C:23]2[CH:27]=[C:28]([F:31])[CH:29]=[CH:30][C:22]=2[O:21][C@@H:20]1[CH:32]1[CH2:34][CH2:33]1>>[CH:32]1([C@@H:20]2[C@H:19]([NH:18][C:3](=[O:5])[C:2]([OH:1])([CH3:17])[C:6]([NH:8][CH2:9][C:10]([F:16])([F:15])[C:11]([F:14])([F:13])[F:12])=[O:7])[C:25](=[O:26])[NH:24][C:23]3[CH:27]=[C:28]([F:31])[CH:29]=[CH:30][C:22]=3[O:21]2)[CH2:34][CH2:33]1

Participants

3

Reactant 2

HCID 21091408HCID 21091408, compoundHCID 67076824(6R,7S)-7-Amino-6-cyclopropyl-2-fluoro-6,7-dihydro-9H-5-oxa-9-aza-benzocyclohepten-8-one

Product 1

HCID 11605452(-)-n-((6r,7s)-6-Cyclopropyl-2-fluoro-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)-2-hydroxy-2-methyl-n'-(2,2,3,3,3-pentafluoro-propyl)-malonamide

Procedure

N-((6R,7S)-6-Cyclopropyl-2-fluoro-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)-2-hydroxy-2-methyl-N′-(2,2,3,3,3-pentafluoro-propyl)-malonamide was obtained as mixture of epimers according to the procedures described for example 2b using racemic 2-hydroxy-2-methyl-N-(2,2,3,3,3-pentafluoro-propyl)-malonamic acid and (6R,7S)-7-amino-6-cyclopropyl-2-fluoro-6,7-dihydro-9H-5-oxa-9-aza-benzocyclohepten-8-one. The epimers were separated by chromatography on Chiralpak AD using isopropanol/heptane 15:85 to yield (−)-N-((6R,7S)-6-cyclopropyl-2-fluoro-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)-2-hydroxy-2-methyl-N′-(2,2,3,3,3-pentafluoro-propyl)-malonamide, entity A, MS m/e (%): 484.5 (M+H+, 100), as first eluting fraction, and (−)-N-((6R,7S)-6-cyclopropyl-2-fluoro-8-oxo-6,7,8,9-tetrahydro-5-oxa-9-aza-benzocyclohepten-7-yl)-2-hydroxy-2-methyl-N′-(2,2,3,3,3-pentafluoro-propyl)-malonamide, entity B, as second eluting fraction, MS m/e (%): 484.5 (M+H+, 100).

Workup

  1. customThe epimers were separated by chromatography on Chiralpak AD

Sources & evidence

ORD record
ord-1fd2581a455642968ba061dcc5526b46
Source dataset
uspto-grants-2007_05
Patent number
US07211573B2

Reaction notes

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