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

HRID 930281Notes

Reaction equation

C([NH:9][C:10]1[O:11][C@H:12]([C:36]([F:39])([F:38])[F:37])[CH2:13][C@:14]([C:18]2[CH:19]=[C:20]([NH:25][C:26]([C:28]3[CH:33]=[N:32][C:31]([O:34][CH3:35])=[CH:30][N:29]=3)=[O:27])[CH:21]=[CH:22][C:23]=2[F:24])([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:36]([F:37])([F:39])[F:38])[CH2:13][C@:14]([C:18]2[CH:19]=[C:20]([NH:25][C:26]([C:28]3[CH:33]=[N:32][C:31]([O:34][CH3:35])=[CH:30][N:29]=3)=[O:27])[CH:21]=[CH:22][C:23]=2[F:24])([CH2:16][F:17])[N:15]=1

Participants

Conditions

Temperature: 75 °C

Procedure

A microwave vial was charged with N-(3-((4S,6S)-2-benzamido-4-(fluoromethyl)-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-methoxypyrazine-2-carboxamide (0.11 g, 0.200 mmol, step 1). MeOH (2 ml) was added followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (0.122 g, 0.801 mmol, Aldrich). The vial was sealed and heated to 75° C. in a microwave (Biotage Initiator) for 1.5 hours. The reaction was cooled to RT and concentrated under reduced pressure. The crude material was purified via silica gel flash chromatography using a gradient of 5-70% EtOAc in hexanes to afford the title compound as a white solid (0.0741 g, 0.166 mmol, 83% yield). MS m/z=446.0 [M+H]+. Calculated for C18H16F5N5O3: 445.343

Workup

customThe vial was sealed
temperatureThe reaction was cooled to RT
concentrationconcentrated under reduced pressure
customThe crude material was purified via silica gel flash chromatography

Sources & evidence

ORD record: ord-681bbc7f3a9f41c79610cbce4a9b5bf4
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296734B2

Reaction notes

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