Preparation of 1-phenylcyclopropylmethylamine_Kain Industrial Additive

Background and overview^[1]

1-Phenylcyclopropylmethylamine can be used as a pharmaceutical synthesis intermediate. If 1-phenylcyclopropanemethylamine is inhaled, please move the patient to fresh air; if there is skin contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical treatment if you feel uncomfortable; if the eyes are clear In case of contact, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

Preparation^[1]

The preparation of 1-phenylcyclopropanemethylamine is as follows: add lithium aluminum hydride (23g, 0.35mol, 1.03 equivalent) to 1-phenylcyclopropanenitrile (50g, 0.34mol, 1 equivalent) at 0°C. Tetrahydrofuran (500mL, 0.7M) solution. The reaction mixture was stirred at 0°C for 1 hour and then at reflux for 1 hour. The reaction mixture was then cooled and quenched with water (23 mL) and 15% aqueous sodium hydroxide solution (69 mL). The mixture was filtered and concentrated in vacuo to give 1-phenylcyclopropylmethylamine (36 g, 72%). LC-MS: m/z148.1[M+H⁺], retention time = 0.86 minutes; ¹HNMR (400MHz, CDCl₃ )δ7.2-7.4(m, 5H), 2.78(s, 2H), 1.19(brs, 2H), 0.72-0.84(m, 4H).

Apply^[1]

1-Phenylcyclopropylmethylamine can be used as a pharmaceutical synthesis intermediate. For example, synthesize (2S)-2-[(1R, 2R)-1-methoxy-2-methyl-3-oxo-3-{[(1-phenylcyclopropyl)methyl]amino}propane base]pyrrolidine-1-carboxylic acid tert-butyl ester. From 11 (2.15 g, 7.48 mmol, 1.1 equiv), 1-phenylcyclopropylmethylamine (1.001 g, The crude desired material was synthesized by silica gel chromatography (gradient: 0% to 100), HATU (3.10 g, 8.16 mmol, 1.2 eq) and triethylamine (2.84 mL, 20.4 mmol, 3 eq) % ethyl acetate/heptane) to obtain (2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1-benzene) as a solid cyclopropyl)methyl]amino}propyl]pyrrolidine-1-carboxylic acid tert-butyl ester (1.93 g, 68%). HPLC (Protocol A at 45°C): m/z417.3 [M+H+], retention time = 10.575 minutes; 1HNMR (400MHz, DMSO-d6), presumably a mixture of rotamers: δ7.75-7.81 (m , 1H), 7.20-7.27(m, 4H), 7.12-7.19(m, 1H), 3.33-3.62 and 3.71-3.80 (br multiplet, 4H in total), 3.28(s, 3H), 2.97-3.17(brm , 2H), 2.14-2.24(m, 1H), 1.67-1.80(brm, 2H), 1.45-1.65(m, 2H), 1.41(s, 9H), 1.00(d, J=6.6Hz, 3H), 0.67-0.93 (m, 4H).

Main reference materials

[1] CN201280056617.4 Cytotoxic peptide and its antibody-drug conjugate