1-Boc-hexahydro-1,4-diazepine

Colorless to yellow liquid

To a solution of di-tert-butyldicarbonate (2.201 g, 9.780 mmol) in acetic acid (9.8 mL), a solution of 1, 4-diazepane (1.0 g, 9.780 mmol) in acetic acid (9.8 mL)at ambient temperature is added. After 24 hours, add water and adjust the pH to 10 with 10percent NaOH. Extract the aqueous phase with dichloromethane (2 x 15 mL), dry the organic phase and eliminate the solvent, to obtain the compound tert-butyl 1, 4-diazepane-1-carboxylate with 90.0percent yield.; A liquid is obtained that was analyzed, obtaining the following data: IR νTo a solution of 1, 4-diazepane (1.00 g, 9.98 mmol) in DCM (22 mL) was added a solution of (t-Boc)c To a solution of homopiperazine 39 (4.01 g, 39.9 mmol, 2 equiv.) in dry dichloromethane (100 mL) at RT was added a solution of Boc[00401] 1. A solution of di-tert-butyl dicarbonate (25 g, 115 mmol.) in CHHomopiperazine (5.00 g, 49.92 mmol) was dissolved in methanol (200 ml) and cooled to 0°C. Boc anhydride (12 g, 55.0 mmol) in methanol (100 ml) was added dropwise over 1 h and the reaction allowed to warm to room temperature after which the reaction was heated to reflux for 4 h. The reaction was concentrated in vacuo and dissolved in 1 M citric acid (150 ml). The aqueous layer was then washed with EtOAc (3 x 70 ml). The aqueous layer was then cooled to 0°C made basic with solid NaAfter homopiperazine 340.0g (3.4mol, 1.5eq), 200mL of ethanol and 50mL of water were mixed, ice water was cooled to 15°C, and then a solution of tert-butyl azide in isopropyl ether was added dropwise thereto. After incubation, the reaction was incubated for 4 h and TLC detected the end of the reaction. After the reaction mixture was concentrated, 200 mL of water was added to stir, and the mixture was filtered. The filtrate was extracted three times with 200 mL of dichloromethane. The combined organic phases were washed once with 200 mL of water and 100 mL of saturated brine in that order, and the organic phase was dried and concentrated to give crude Boc-protected homopiperazine. 250 mL of petroleum ether was added to the crude product and stirred. The solid was washed with ice-cold salt and dried. After suction drying, a single Boc-protected homopiperazine was obtained. The yield was 313.2 g, and the GC purity was 97.2percent. The yield is 68.9percent.

1-Boc-hexahydro-1,4-diazepine is a diazepine derivative used in the preparation of pharmaceutical compounds such as histamine H3-receptor antagonists and dipeptidyl peptidase IV (DPP-IV) inhibitors.

Molecular Weight:200.28
XLogP3:0.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:200.152477885
Monoisotopic Mass:200.152477885
Topological Polar Surface Area:41.6
Heavy Atom Count:14
Complexity:199
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes