[C:1]([Cl:6])(=O)[C:2](Cl)=[O:3].[ClH:7].[CH:8]1([C@H:11]([NH:15][CH2:16][C:17]#[N:18])[CH2:12][O:13][CH3:14])[CH2:10][CH2:9]1>O1CCOCC1.C(Cl)Cl>[Cl:6][C:1]1[C:2](=[O:3])[N:15]([C@@H:11]([CH:8]2[CH2:10][CH2:9]2)[CH2:12][O:13][CH3:14])[CH:16]=[C:17]([Cl:7])[N:18]=1Oxalyl chloride (54.5 mL, 624 mmol) was added dropwise to a cold (<8° C.) solution of (S)-2-(1-cyclopropyl-2-methoxyethylamino)acetonitrile hydrochloride (23.6 g, 124 mmol) in 1,4 dioxane (300 mL) and methylene chloride (200 mL). The reaction mixture was then heated at 53° C. for 19 h. The reaction mixture was cooled to room temperature and concentrated to a semi-solid then co-evaporated three times with CH2Cl2 (50 mL). The resulting brown solid was purified by column chromatography on silica gel (0→10%→20% ethyl acetate in hexanes) to afford (S)-3,5-dichloro-1-(1-cyclopropyl-2-methoxyethyl)pyrazin-2(1H)-one (22.4 g, 69% yield) as a white solid: mp 109.8-110.8° C.; [α]25D −88.8 (c 0.513, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.54 (s, 1H), 4.12-4.08 (m, 1H), 3.73 (dd, JAB=10.3, JAX=4.5 Hz, 1H), 3.62 (dd, JBA=10.3, JBX=3.0 Hz, 1H), 3.32 (s, 3H), 1.43-1.37 (m, 1H), 0.82-0.76 (m, 1H), 0.65-0.61 (m, 1H), 0.55-0.50 (m, 1H), 0.33-0.27 (m, 1H); LRMS (ESI) m/e 206.3 [(M+H)+, calcd for C10H13N2O2Cl2 263.0]. Anal. calcd. for C10H12N2O2Cl2: C, 45.64; H, 4.59; N, 10.64. Found: C, 45.74; H, 4.62; N, 10.61.
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