ChemicalBook CAS DataBase List 4-(Boc-Aminomethyl)piperidine

4-(Boc-Aminomethyl)piperidine synthesis

6synthesis methods

Product Name:4-(Boc-Aminomethyl)piperidine
CAS Number:135632-53-0
Molecular formula:C11H22N2O2
Molecular Weight:214.3

7144-05-0 Synthesis

7144-05-0
210 suppliers
$6.00/1g

49761-82-2 Synthesis

49761-82-2
138 suppliers
$5.00/1g

135632-53-0
228 suppliers
$21.00/1g

Yield:135632-53-0 70%

Reaction Conditions:

in toluene at 25;

Steps:

227
A solution of piperidinyl-4-methylamine (3.6 g) and N-tert-butoxycarbonylimidazole (5.3 g) in toluene (80 mL) was stirred at 25° C. overnight. The solution was then concentrated and the resultant residue was purified by column chromatography on silica gel (EtOAc/Hexane=1/2) to give Intermediate 227-I (4.7 g) in a 70% yield. Intermediate 227-I (4.7 g) and Et₃N (2.7 mL) in 1-pentanol (20 mL) was reacted with 2,4-dichloro-6-aminopyrimidine (5.4 g) at 120° C. for 12 hours. After the solvent was removed, the residue was purified by column chromatography on silica gel (EtOAc/Hexane=1/9) to afford Intermediate 227-II (5.2 g) in a 70% yield. A solution of Intermediate 227-II (1.0 g) treated with 1 M HCl (20 mL) in CH₂Cl₂(10 mL) was stirred at room temperature for 8 hours. After the solution was concentrated, the resultant residue was neutralization with NH₄OH, and extracted with CH₂Cl₂. The organic layer was separated and concentrated. The residue thus obtained was purified by column chromatography on silica gel (using MeOH as an eluant) to afford Intermediate 227-III (636 mg) in a 90% yield. Intermediate 222-III (790 mg) prepared from Example 222 was added to a solution of Intermediate 227-III (450 mg) in MeOH (20 mL). The mixture was stirred at 25° C. for 2 hours. NaBH(OAc)₃(2.0 g) was then added at 25° C. for 12 hours. After the solution was concentrated, a saturated aq. NaHCO₃solution was added to the resultant residue. The mixture was then extracted with CH₂Cl₂. The organic layer was separated and concentrated. The residue thus obtained was purified by column chromatography on silica gel (using MeOH as an eluant) to afford Intermediate 227-IV (539 mg) in a 60% yield. N¹-Morpholine-N¹-piperazine ethane (240 mg) was added to a solution of Intermediate 227-IV (160 mg) in 1-pentanol (1 mL). The mixture was stirred at 120° C. for 8 hours. The solution was concentrated and the residue was purified by column chromatography on silica gel (EtOAc/MeOH=5/1) to afford Intermediate 227-V (85 mg) in a 40% yield. A solution of 20% TFA/CH₂Cl₂(1 mL) was added to a solution of Intermediate 227-V (85 mg) in CH₂Cl₂(1 mL). The reaction mixture was stirred for 8 hours at room temperature and concentrated by removing the solvent. The resultant residue was purified by column chromatography on silica gel (21% NH₃(aq)/MeOH=1/19) to afford Compound 227 (65 mg) in a 90% yield. Compound 227 was then treated with 1 M HCl (1 mL) in CH₂Cl₂(1 mL) for 0.5 hour. After the solvents were removed, the residue was treated with ether and filtered to give hydrochloride salt of Compound 227. CI-MS (M⁺+1): 544.4.

References:

Yen, Chi-Feng;Hu, Cheng-Kung;Chou, Ming-Chen;Tseng, Chen-Tso;Wu, Chien-Huang;Huang, Ying-Huey;Chen, Shu-Jen;King, Chi-Hsin Richard US2006/281712, 2006, A1 Location in patent:Page/Page column 108-109

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