1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluoro-N-((S)-1-methoxypropan-2-yl)benzamide

HRID 930411Notes

Reaction equation

C([NH:9][C:10]1[O:11][C@H:12]([C:33]([F:36])([F:35])[F:34])[CH2:13][C@:14]([C:18]2[CH:19]=[C:20]([CH:29]=[CH:30][C:31]=2[F:32])[C:21]([NH:23][C@@H:24]([CH3:28])[CH2:25][O:26][CH3:27])=[O:22])([CH2:16][F:17])[N:15]=1)(=O)C1C=CC=CC=1.N12CCCN=C1CCCCC2>CO>[NH2:9][C:10]1[O:11][C@H:12]([C:33]([F:36])([F:35])[F:34])[CH2:13][C@:14]([C:18]2[CH:19]=[C:20]([CH:29]=[CH:30][C:31]=2[F:32])[C:21]([NH:23][C@@H:24]([CH3:28])[CH2:25][O:26][CH3:27])=[O:22])([CH2:16][F:17])[N:15]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of 3-((4S,6S)-2-benzamido-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluoro-N-((S)-1-methoxypropan-2-yl)benzamide (0.0591 g, 0.115 mmol) in MeOH (1.15 mL) was added 1,8-diazabicyclo-[5.4.0]undec-7-ene (0.021 ml, 0.138 mmol) and allowed to stir at 65° C. for 15 h. The reaction mixture was concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage SNAP Ultra silica gel column (25 g), eluting with a gradient of 20-100% EtOAc in hexane, to provide 3-((4S,6S)-2-amino-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluoro-N-((S)-1-methoxypropan-2-yl)benzamide (0.0246 g, 0.060 mmol, 52.2% yield). MS m/z=410.0 [M+H]+. Calculated for C17H20F5N3O3: 409.14

Workup

concentrationThe reaction mixture was concentrated in vacuo
customchromatographed through a Biotage SNAP Ultra silica gel column (25 g)
washeluting with a gradient of 20-100% EtOAc in hexane

Sources & evidence

ORD record: ord-79cbde0f908644269d643a89f115a78e
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296734B2

Reaction notes

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