5-Chloro-2,4-difluorobenzenemethanamine

10489] A 50-mE 1-neck round bottom flask was charged with reactant 15-A (0.015 g, 0.047 mmol, the synthesis of 15-A is described in example 41), (5-chioro-2, 4-difluorophe- nyl)methanamine (0.009 g, 0.05 mmol), DIPEA (0.06 g, 0.47 mmol) and HATU (0.035 g, 0.09 mmol) in DCM (3 ml). The reaction mixture was stirred at room temperature for 1 hout The reaction mixture was concentrated down, re-dissolved in EtOAc (50 mE), washed with saturated NaHCO3 twice, washed with saturated NH4C1 and dried over Na2 SO4. After concentration, the crude was purified by column chromatography on silica gel with hexane-EtOAc to obtain 15-B. ECMS-ESI (mlz): [M+H]. found: 483.Example 80 Preparation of Compound 8Theta (1 R, 4S, 12a )-N-(5-chloro-2, 4-difluorobenzyl)-7-hydroxy-6, 8-dioxo- 1 , 2, 3, 4, 6, 8, 12, 12a- octahydro-l , 4-methanodipyrido[l , 2-a: r, 2'-d]pyrazine-9-carboxamide 80 Step 1 A 50-mL round bottom flask was charged with 80-A (0.12 g, 0.32 mmol), (5-chloro-254-difluorophenyl)methanamme (0.1. 1 g, 0.63 mmol), N, N~ diisopropylethy famine (DIPEA) (0.20 g, 1.58 mmol) and HATU (0.24 g, 0.63 mmol) in EX 1 ( .10 ml). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated down, re-dissolved in EtOAc (50 raL), washed with saturated NaHCOj (2x), saturated NH4CI and dried over Na2S04. After concentration, the crude was purified by column chromatography on silica gel with hexane-EtOAc to obtain 80-B as a white solid. LCMS-ES ini/z): j VI · i | ; found: 541 .N-(5-Chloro-2, 4-difluorobenzyl)-2, 2-dimethoxyacetamide; A mixture of methyl dimethoxyacetate (1.45 g, 10.7 mmol) and

Molecular Weight:177.58
XLogP3:1.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:177.0156832
Monoisotopic Mass:177.0156832
Topological Polar Surface Area:26
Heavy Atom Count:11
Complexity:134
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes