Methyl 2-[2-(tert-butoxycarbonylamino)-1,3-benzothiazole-6-carboxamido]acetate

In the title compound, C16H19N3O5S, the dihedral angle between the benzene ring and the carbonylamino group is 18.18 (2)°. In the crystal, molecules form centrosymmetric dimers via pairs of N—H⋯N hydrogen bonds. The dimers are connected via N—H⋯O hydrogen bonds into a three-dimensional network..

In the title compound, C 16 H 19 N 3 O 5 S, the dihedral angle between the benzene ring and the carbonylamino group is 18.18 (2) . In the crystal, molecules form centrosymmetric dimers via pairs of N-HÁ Á ÁN hydrogen bonds. The dimers are connected via N-HÁ Á ÁO hydrogen bonds into a threedimensional network..   Table 1 Hydrogen-bond geometry (Å , ).

Comment
Benzothiazole is a heterocyclic compound, which contains a benzene ring and a thiazole ring, and is a component of a lot of natural products, biological pesticides, drugs, spices and so on. The benzothiazole derivatives have broad biological activities that make them play an important role in drug research and development. For example, they showed anti-tumor (Brantley et al., 2004;Mortimer et al., 2006;Ćaleta et al., 2009) and anti-microbial activities (Palmer et al., 1971). During our development of 2-aminobenzothiazole-based Urokinase-Type Plasminogen Activator (uPA) inhibitors, we synthesized the title compound (I) as an intermediate. The compound (I) has certain biological activity, and its IC50 is 780 µM as uPA inhibitor itself.
The molecule structure of the title compound (I) is shown in Fig. 1. The molecular skeleton is slightly distorted from a planar conformation with the angle between benzene and thiazole rings of 1.46 (1)°. And for the substituents, the dihedral angles between the thiazole ring and tert-butyl carbamate is 9.15 (6)°, the dihedral angles between benzene ring and carbonylamino group is 18.18 (2)°, and the dihedral angles between carbonylamino group and methyl acetate is 79.24 (3)°.
In the crystal, there are intermolecular hydrogen bonds of N1-H1···N2 and N3-H3···O3. Where, two molecules form a pair with inversion symmetry via N-H···N hydrogen bonds, and the pairs form a three dimensional network via N-H···O hydrogen bonds. No π-π interactions are found in this structure.

Experimental
In a 250 ml round bottom flask, the pale yellow solid of ethyl 2-(tert-butoxycarbonylamino) benzothiazole-6-carboxylate, N-Boc ester (3.22 g, 10 mmol) in a mixed solution of EtOH (100 ml) and 2 N aq NaOH (80 ml) were refluxed for 5 h. Then the solution was cooled with an ice bath and acidified with 1 N aq HCl, when pH<2, white floc generated and put it aside for 2 h. Then the mixture was filtered and the filter mass was washed to neutral by water and dried to afford white solid of 2-(tert-butoxycarbonylamino)benzothiazole-6-carboxylic acid, N-Boc acid (2.59 g, yield: 88%).
Then the reaction solution was pured into 200 mL of 10% Na 2 CO 3 solution and stirred for 1 h. The precipitate was filtered, washed with water, and dried to give the white solid of title compound (I) (591 mg, yield: 81%).
The solid was dissolved by DMF and filtered. The DMF was evaporated slowly at room temperature for 15-20 days, and colorless sheetlike crystals suitable for X-ray structure analysis were separated from the solution.
supplementary materials sup-2 Refinement All hydrogen atoms were positioned geometrically and refined in a riding model approximation with U iso (H) = 1.2 or 1.5 U eq (C). Fig. 1. A view of the molecular structure of (I), with displacement ellipsoids drawn at the 50% probability level for non-H atoms. as those based on F, and R-factors based on ALL data will be even larger.