1-Boc-4-ethynylpiperidine

At 0 C, to a stirred mixture of 4-formyl-piperidine-1-carboxylic acid tert-butyl ester (358 mg, 1.68 mmols) and potassium carbonate (464 rng, 3.36 mmols) in methanol (16 ml) was added dropwise a solution of (1-diazo-2-oxo-propyl)- phosphonic acid dimethyl ester (323 mg, 1.68 mmols) in methanol (2 ml). The resulting mixture was stirred at room temperature overnight, filtered and concentrated. The residue was chromatographed on silica gel using a solution of ethyl acetate in hexanes (1:5) to provide the title compound (308 mg, 88percent) as colorless crystals. LCMS m/e (154, M - M3u + 2H). (J. Am. Chem. Soc. 2003, 125, 3714.)At 0 C, to a stirred mixture of 4-formyl-piperidine-1-carboxylic acid fert-butyl ester (358 mg, 1.68 mmols) and potassium carbonate (464 mg, 3.36 mmols) in methanol (16 ml) was added dropwise a solution of (1-diazo-2-oxo-propyl)- phosphonic acid dimethyl ester (323 mg, 1.68 mmols) in methanol (2 ml). The resulting mixture was stirred at room temperature overnight, filtered and concentrated. The residue was chromatographed on silica gel using a solution of ethyl acetate in hexanes (1 :5) to provide the title compound (308 mg, 88percent) as colorless crystals. LCMS m/e (154, M - f-Bu + 2H). (J. Am. Chem. Soc. 2003, 725, 3714.)A solution of compound 7 (0.1 g, 0.41 mmol) in methanolwas stirred at room temperature for 10 min. Then compound8 (95 mg, 0.49 mmol) and K2CO3 (113 mg, 0.82 mmol) were added and stirred at room temperature for 18 h. Thereaction mixture was filtered through a celite pad to removeK2CO3. The solvent was evaporated under vacuum. Thenwater was added and the product was extracted by ethylacetate (3 × 30 ml). The crude material was purified bycolumn chromatography to obtain product. Compound 9 Yield 81percent, white solid powder; MS: [M+H]+ 210.09; 1H-NMR (400MHz, CDCl3-D) δ 3.72 (m, 2H), 3.20 (m, 2H), 2.06 (s, 1H), 2.12 (d, J = 2.4 Hz, 1H), 1.81(m, 2H), 1.60 (m, 2H), 1.47 (s, 9H). 13C-NMR (100MHz, CDCl3-D) δ 154.8, 86.4, 79.5, 69.5, 31.2, 28.4, 26.7.Example 124; Preparation of tert-butyl 4-(2-(7-(4-(1-(carbamoyl)cyclopropanecarboxamido)-2-fluorophenoxy)thieno[3, 2-b]pyridin-2-yl)ethynyl)piperidine-1-carboxylate; Step A: Preparation of tert-butyl 4-ethynylpiperidine-1-carboxylate; To a stirred suspension of tert-butyl 4-formylpiperidine-1-carboxylate (0.427 g, 2.00 mmol), K

Molecular Weight:209.28
XLogP3:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:209.141578849
Monoisotopic Mass:209.141578849
Topological Polar Surface Area:29.5
Heavy Atom Count:15
Complexity:274
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes