2-METHYL-1,3-BENZOXAZOLE-5-CARBOXYLICACID

To a solution of methyl 2-methylbenzo[d]oxazole-5-carboxylate (0.50 g, 2.6 mmol) in tetrahydrofuran/methanol/water (1: 1 : 1, 15 mL) was added lithium hydroxide hydrate (0.22 g, 5.2 mmol). The resulting mixture was stirred at 25 °C for 3 hours. On completion, the mixture was acidified by hydrochloric acid, resulting in formation of a solid. The solid was collected by filtration, washed with water and dried in vacuo. The residue was purified by silica gel chromatography [petroleum ether: ethyl acetate = 1 : 1] to give compound B-129 (0.30 g, 65percent yield) as a white solid.2-methyl benzooxazol-5-carboxylic acid: A mixture of 3-amino-4-hydroxybenzoic acid (1.5 g, 9.79 mmol) and trimethyl orthoacetate (15 mL, large excess) was heated at 65° C. for 5 hrs under argon. The reaction mixture was cooled to room temperature, filtered, washed with hexanes. The filtrate was concentrated in vacuo to afford the product as a yellow solid (1.4 g, 80percent): N-((3R)-1-((3-(cyclopropylmethyl)-7-fluoro-1-isopropyl-2, 4-dioxo-1, 2, 3, 4-tetrahydroquinazolin-6-yl)carbamoyl)piperidin-3-yl)-2-methyl-1, 3-benzoxazole-5-carboxamide HATU (70.4 mg, 0.19 mmol) was added to a solution of (R)-3-amino-N-(3-(cyclopropylmethyl)-7-fluoro-1-isopropyl-2, 4-dioxo-1, 2, 3, 4-tetrahydroquinazolin-6-yl)piperidine-1-carboxamide hydrochloride (70 mg, 0.15 mmol), Following general procedure B, Compound (i?-32 was prepared from compound B-129 (69 mg, 0.39 mmol) and compound (i?)-A-104 (50 mg, 0.32 mmol), with a reaction time of 12 hours. The product was purified by prep-HPLC [Instrument: GX-C; Column: Phenomenex Gemini CI 8 150x30 mm, particle size: 5 mupiiota; Mobile phase: 35-65percent acetonitrile in H20 (add 0.5percent NH3 H20, v/v)] to give: (R)-N-(2, 2 -dimethylquinuclidin-3 -yl) -2-methylbenzo [d] oxazole -5 -carboxamide (compound (i?)-32) (30 mg, 30percent yield) as a white solid: cSFC analytical (A) tR=2.44 min., purity: 96.08percent; LCMS (J): tR=0.995 min., 314.1 m/z (M+1); -NMR (CD3OD, 400 MHz): delta 8.10 (s, IH), 7.87-7.85 (m, IH), 7.67 (d, J=8.8 Hz, IH), 4.07 (s, IH), 3.33-3.33 (m, 2H), 2.85-2.85 (m, 2H), 2.69 (s, 3H), 2.09-2.09 (m, IH), 1.97-1.86 (m, 3H), 1.67-1.64 (m, IH), 1.51 (s, 3H), 1.32 (s, 3H).To a solution of methyl 2-methylbenzo[d]oxazole-5-carboxylate (0.50 g, 2.6 mmol) in tetrahydrofuran/methanol/water (1: 1 : 1, 15 mL) was added lithium hydroxide hydrate (0.22 g, 5.2 mmol). The resulting mixture was stirred at 25 °C for 3 hours. On completion, the mixture was acidified by hydrochloric acid, resulting in formation of a solid. The solid was collected by filtration, washed with water and dried in vacuo. The residue was purified by silica gel chromatography [petroleum ether: ethyl acetate = 1 : 1] to give compound B-129 (0.30 g, 65percent yield) as a white solid.To a flask containing Step 2 - Preparation of Intermediate E Step 2 - Preparation of Intermediate H Preparation of

Molecular Weight:177.16
XLogP3:1.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:177.042593085
Monoisotopic Mass:177.042593085
Topological Polar Surface Area:63.3
Heavy Atom Count:13
Complexity:219
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes