Dimethyl Sulfoxide → tert-butyl (2R)-2-[(6-chloropyrazin-2-yl)amino]propanoate

HRID 510187Notes

Reaction equation

Cl[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([Cl:8])[N:3]=1.Cl.[C:10]([O:14][C:15](=[O:19])[C@@H:16]([CH3:18])[NH2:17])([CH3:13])([CH3:12])[CH3:11].CS(C)=O.CCN(C(C)C)C(C)C>C(OCC)(=O)C>[Cl:8][C:4]1[N:3]=[C:2]([NH:17][C@H:16]([CH3:18])[C:15]([O:14][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:19])[CH:7]=[N:6][CH:5]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a reaction vessel was added 2,6-dichloropyrazine (CA, 492 mg, 3.30 mmol), D-Alanine tert-butyl ester hydrochloride (Aldrich Chemical) (500 mg, 2.75 mmol), DMSO (3 mL) and DIPEA (1.923 mL, 11.01 mmol). The resulting solution was heated to 120° C. for 18 hrs. The reaction mixture was cooled and diluted with ethyl acetate (30 mL). The organic layer was washed with aqueous sodium hydrogen carbonate followed by aq. brine. The aqueous layers were back extracted with ethyl acetate and the combined organic layers dried with sodium sulfate, filtered and concentrated to give an oil. The residue was purified by silica gel chromatography on Biotage 50 g SNAP column, eluting with EtOAc/Hexane (10-60%) to give the product, I-9, as a yellow oil. (663 mg, 93%) LRMS (ESI) m/z 258.1 [(M+H)+; calcd for C11H16ClN3O2: 258.1].

Workup

temperatureThe reaction mixture was cooled
washThe organic layer was washed with aqueous sodium hydrogen carbonate
extractionThe aqueous layers were back extracted with ethyl acetate
dry with materialthe combined organic layers dried with sodium sulfate
filtrationfiltered
concentrationconcentrated
customto give an oil
customThe residue was purified by silica gel chromatography on Biotage 50 g SNAP column
washeluting with EtOAc/Hexane (10-60%)
customto give the product, I-9

Sources & evidence

ORD record: ord-03b90a0008384bc4902bf7f67259f55a
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09096598B2

Reaction notes

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