supplementary materials

Compounds containing boronic acids [RB(OH)₂] or boronate esters [RB(OR')₂] have found remarkable synthetic utility in Suzuki-Miyaura cross coupling reactions (Miyaura and Suzuki, 1995) over the past decade. Interest in these compounds also arises from their diverse and potent biological activities (Yang et al., 2003). Indeed, we have recently shown that dihydropyrimidinones (Biginelli products) containing boronic acids show significant promise for their ability to inhibit the MCF7 breast cancer cell line (Blacquiere et al., 2005). Biginelli compounds containing thiophenes showed the most promise in this study. Some of the biological properties of boron compounds have been attributed to the ability of the three-coordinate boron atom to form bonds with biomolecules, as well as form hydrogen bonds with the adjacent O atoms of the boronic acid or boronate ester group. We are preparing a family of boron-containing Biginelli products in order to understand the mechanism of action of these compounds in an effort to design more potent candidates.

The title compound crystallizes with two independent molecules per asymmetric unit. In one of the independent molecules the ester group is coplanar with the pyrimidine ring [torsion angles: C40—C48—O50—C51 = 177.11 (13)° and C48—O50—C51—C52 = 179.83 (16)°], the second independent molecule shows rotation of the ethyl group of the ester moiety that displaces the methyl group from the pyrimidine ring plane [torsion angles: C10—C18—O20—C21 = -179.33 (13)° and C18—O20—C21—C22 = -81.2 (2)°]. Conversely, the latter molecule displays coplanar dioxaborolane and thiophene rings [torsion angles: C2—C1—B1—O2 = 6.2 (3)° and S1—C1—B1—O1 = 3.4 (2)°], while the former shows rotation about the inter-ring linkage [torsion angles: C32—C31—B31—O32 = 20.9 (2)° and S3—C31—B31—O31 = 24.7 (3)°]. However, these torsion angles allow for orbital overlap between the boron p_z orbital and the aryl π-electron system. The Bpin skeleton displays similar bond lengths and angles as found in related aniline derivatives (Vogels et al., 2006). Although steric crowding at the boron center is not present, the title compound shows no appreciable intra- or intermolecular Lewis acid-base interactions. However, hydrogen bonding is observed for all N—H groups of the 3,4-dihydropyrimidine-2(1H)-thione fragment. Two NH···O bonds are present for H6 and H36 (H6···O49ⁱ = 2.06 Å, (i): x, y - 1, z and H36···O19ⁱⁱ = 2.14 Å. (ii): x - 1, y, z) while two very long NH···S bonds are found for H8 and H38 (H8···S3 = 2.91 Å and H38···S2ⁱⁱⁱ = 2.61 Å, (iii): -x, -y + 1, -z).