1-Boc-3,3-dimethylpiperazine

To a solution of 2, 2-dimethylpiperazine (400 mg) in dichloromethane (20 mL) at 0° C. was added di-tert-butyl dicarbonate (766 mg). Compound (I'-161): To a mixture of 6.02 g (0.01760 mole) of 2, 2-dimethylpiperazine-2 trifluoroacetate, 7.8 ml (0.0563 mole) of triethylamine and 30 ml of tetrahydrofuran was added dropwise 4.2 ml (0.01848 mole) of di-tsrt-butyl dicarbonate under ice-cooling, and the mixture was stirred at room temperature for 3 hours. The reaction solution was concentrated under reduced pressure, and 1N-aqueous HCl and diisopropyl ether were added, and extracted. The aqueous layer was alkalified with 2N-aqueous NaOH, and extracted with ethyl acetate. The organic layer was washed with brine, and dried over anhydrous sodium sulfate, and the solvent was concentrated under reduced pressure to give 2.6 g (69percent) of 1-tert-butoxycarbonyl 3, 3-dimethylpiperazine as a pale yellow liquid. 1H-NMR(CDCl3): δ(ppm) 1.11 (6H, s), 1.46 (9H, s), 2.87 (2H, t, J=5Hz), 3.16 (2H, s), 3.36 (2H, t, J=5Hz).8-tert-butyl-6-(4-fluorophenyl)imidazo[l, 2-b]pyridazine-2-carboxylic acid (5g, 16 mmol), DMF (l20mL), HATU (7.3g, 19.2 mmol), tert-butyl 3, 3 -dimethylpiperazine-l -carboxylate (4.lg, 1.92 mmol) and DIPEA (lOmL, 57.4 mmol) afforded tert-butyl 4-(8-(tert-butyl)-6- (4-fluorophenyl)imidazo [l, 2-b]pyridazine-2-carbonyl)-3 , 3 -dimethylpiperazine- 1 - carboxylate that was dissolved in 4N HC1 solution in l, 4-dioxane (60 mL) affording 4-(8- (tert-butyl)-6-(4-fluorophenyl)imidazo[l, 2-b]pyridazine-2-carbonyl)-3, 3- dimethylpiperazine hydrochloride (6.5g, 97%) as a solid. 1H NMR (401 MHz, DMSO) d 9.71 (bs, 2H), 8.57 (s, 1H), 8.17 - 8.10 (m, 2H), 7.50 (s, 1H), 7.44 - 7.36 (m, 2H), 4.16 - 4.08 (m, 2H), 3.35 - 3.27 (m, 2H), 3.23 - 3.14 (m, 2H), 1.61 (s, 6H), 1.59 (s, 9H).To a stirred solution of To a stirred solution of amine compound 2(0.5 g, 1 eq) and aldehyde 1(0.421 g, 1.1 eq) in DCM (10 mL), sodium triacetoxyborohydride (STAB) (0.693 g, 1 .4 eq) was added. The reaction mixture was stirred at room temperature for overnight; the reaction progress was monitored by TLC and LCMS. After completion of reaction, the reaction mixture was partitioned between DCM and water. The organic layers were separated, washed with water and brine, dried over Na2504 and evaporated to get the crude product which was purified by silica gel column chromatography to afford the desired compound 3.

Molecular Weight:214.30
XLogP3:1.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:214.168127949
Monoisotopic Mass:214.168127949
Topological Polar Surface Area:41.6
Heavy Atom Count:15
Complexity:244
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes