tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate synthesis

4synthesis methods

Product Name:tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate
CAS Number:791852-35-2
Molecular formula:C15H20ClN5O2
Molecular Weight:337.8046

4-[2-[(1,1-dimethylethoxy)carbonyl]hydrazinyl]-1-Piperidinecarboxylic acid 1,1-dimethylethyl ester

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5305-40-8 Synthesis

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tert-butyl 4-(4-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate

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Yield:791852-35-2 70%

Reaction Conditions:

Stage #1: 4-(N'-tert-Butoxycarbonyl-hydrazino)-piperidine-1-carboxylic acid tert-butyl ester;2,6-dichloro-pyrimidine carbaldehydewith N-ethyl-N,N-diisopropylamine in tetrahydrofuran at 0 - 20;
Stage #2: in toluene at 110; for 6 h;

Steps:

19.C

Method C; A solution of 4-(tert-butoxycarbonyl-hydrazino)-piperidine-1-carboxylic acid tert-butyl ester (Intermediate 15; 1.80 g, 5.71 mmol), diisopropylethylamine (2.0 mL, 11.3 mmol), and 4,6-dichloropyrimidine-5-carbaldehyde (Intermediate 16; 1.00 g, 5.65 mmol) in tetrahydrofuran (10 mL) was stirred at 0° C. for 30 min, then it was warmed up to rt and stirred for 4 h. The solid was filtered. The filtrate was washed with brine (10 mL) and the aqueous layer was extracted with methyl tert-butyl ether (1×10 mL). The combined organic layers were washed with brine (1×10 mL) and concentrated to give an orange-red semi-solid. Toluene (10 mL) was added and the solution was heated to 110° C. for 6 h. The reaction mixture was cooled to room temperature and concentrated to give a semi-solid. This crude solid was dissolved in the minimum amount of dichloromethane and passed through a pad of silica gel, eluting with 9% ethyl acetate/hexanes. Concentration of fractions homogeneous for the product gave 4-(4-chloro-pyrazolo[3,4-d]pyrimidin-1-yl)-piperidine-1-carboxylic acid tert-butyl ester (1.33 g, 70%) as a cream white solid. ¹H NMR (CDCl₃) δ 1.49 (s, 9H), 1.9-2.1 (m, 2H), 2.25 (qd, 2H, J=12.6, 4.5 Hz), 2.97 (t, 2H, J=12.0 Hz), 4.30 (br, 2H), 4.96 (tt, 1H, J=11.4, 4.2 Hz), 8.15 (s, 1H), 8.75 (s, 1H).

References:

US2009/286812,2009,A1 Location in patent:Page/Page column 24