Tert-butoxycarbonylalanine → [(S)-1-(3-Bromo-2-cyclopropylamino-4-fluorophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester

HRID 243139Notes

Reaction equation

[Br:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([NH2:9])[C:3]=1[NH:10][CH:11]1[CH2:13][CH2:12]1.[C:14]([O:18][C:19]([NH:21][C@@H:22]([CH3:26])[C:23](O)=[O:24])=[O:20])([CH3:17])([CH3:16])[CH3:15].C1C=NC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[C:14]([O:18][C:19](=[O:20])[NH:21][C@H:22]([C:23](=[O:24])[NH:9][C:4]1[CH:5]=[CH:6][C:7]([F:8])=[C:2]([Br:1])[C:3]=1[NH:10][CH:11]1[CH2:13][CH2:12]1)[CH3:26])([CH3:15])([CH3:16])[CH3:17]

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of 3-bromo-N2-cyclopropyl-4-fluorobenzene-1,2-diamine (759 mg, 3.10 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (644 mg, 3.41 mmol), HOAt (464 mg, 3.41 mmol) and N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (654 mg, 3.41 mmol) in DCM (20 mL) was stirred at 0° C. for 1 h. The reaction mixture was then partitioned between DCM and a saturated solution of NaHCO3. The organic fraction was dried and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane) to afford the title compound (1.05 g, 81%) as a pale beige solid. LCMS (Method C): RT 3.66 min [M+H]+ 416.05

Workup

customThe reaction mixture was then partitioned between DCM
customThe organic fraction was dried
concentrationconcentrated in vacuo
customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane)

Sources & evidence

ORD record: ord-78ae5010312d45bd813dcf735c14ec4a
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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