(S)-2-tert-butoxycarbonylaminopropionimidic acid ethyl ester → [(S)-1-((S)-6-Fluoro-3-methyl-3,4-dihydro-5-oxa-1,2a-diazaacenaphthylen-2-yl)ethyl]carbamic acid tert-butyl ester

HRID 243232Notes

Reaction equation

[F:1][C:2]1[C:11]2[O:10][CH2:9][C@H:8]([CH3:12])[NH:7][C:6]=2[C:5]([NH2:13])=[CH:4][CH:3]=1.C(O[C:17](=N)[C@@H:18]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH3:19])C>CCO>[C:24]([O:23][C:21](=[O:22])[NH:20][C@H:18]([C:17]1[N:7]2[C:6]3[C:11]([O:10][CH2:9][C@@H:8]2[CH3:12])=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[N:13]=1)[CH3:19])([CH3:27])([CH3:26])[CH3:25]

Participants

Conditions

Temperature: 75 °C

Procedure

(S)-8-Fluoro-3-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-5-ylamine (160 mg, 0.86 mmol) was added to a solution of (S)-2-tert-butoxycarbonylaminopropionimidic acid ethyl ester (570 mg, 2.64 mmol) in EtOH (10 mL) and the reaction was heated at 75° C. for 60 min. The reaction mixture was concentrated in vacuo, and the residue was partitioned between DCM and sat. NaHCO3. The organic phase was washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0-40% DCM in cyclohexane) to afford the title compound as an off-white foam (220 mg, 76%). LCMS (Method J): RT=2.50 min, [M+H]+=336.

Workup

concentrationThe reaction mixture was concentrated in vacuo
customthe residue was partitioned between DCM and sat. NaHCO3
washThe organic phase was washed with brine
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-3328744f466141baafb0b12154c8ee98
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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