2-Butyl-11-phenyl-5,10-dihydro-1H-benzo[e]imidazo[1,5-a][1,4]diazepine-1,3(2H)-dione

The title compound, C21H21N3O2, was obtained following a five-step synthetic procedure yielding weakly diffracting rod and needle-shaped crystals which crystallized concomitantly. Structural analysis of a rod-shaped crystal showed that the central seven-membered heterocyclic ring adopts a conformation that is perhaps best described as a distorted boat, with the H-bearing (CH2 and NH) atoms lying well out of the least-squares mean plane fitted through the other five atoms in the ring (r.m.s. deviation 0.075 Å). In the crystal, the compound packs as a twisted chain, which propagates along the b axis by means of an R 1 2(6) motif formed by one of the carbonyl O atoms acting as a bifurcated acceptor in an N—H⋯O and C—H⋯O interaction. No diffraction was observed from the needle-shaped crystals.

The title compound, C 21 H 21 N 3 O 2 , was obtained following a five-step synthetic procedure yielding weakly diffracting rod and needle-shaped crystals which crystallized concomitantly. Structural analysis of a rod-shaped crystal showed that the central seven-membered heterocyclic ring adopts a conformation that is perhaps best described as a distorted boat, with the H-bearing (CH 2 and NH) atoms lying well out of the leastsquares mean plane fitted through the other five atoms in the ring (r.m.s. deviation 0.075 Å ). In the crystal, the compound packs as a twisted chain, which propagates along the b axis by means of an R 1 2 (6) motif formed by one of the carbonyl O atoms acting as a bifurcated acceptor in an N-HÁ Á ÁO and C-HÁ Á ÁO interaction. No diffraction was observed from the needle-shaped crystals.

Comment
We recently investigated a three step solution phase protocol for the synthesis of arrays of tricyclic fused hydantoin-benzodiazepines as part of broader research on multi-component reactions ( Figure 1). Interestingly, the major product of this unique synthetic route was the tautomer 5 derived from the originally desired product 4, the structure being confirmed by X-ray crystallography. The methodology employs ortho-N-Boc benzylamines 1 and phenylglyoxaldehydes 2 in the rarely used five component Ugi reaction with CO 2 to assemble desired diversity in product 3 (Hulme et al., 2000). Acid treatment unmasks an internal amino nucleophile and promotes rapid formation of the diazepine ring of generic structure 4. Subsequent base treatment employs the amidic NH of the Ugi scaffold as a second internal nucleophile promoting hydantoin formation and an unexpected 1,3-H shift to give 5. As such the methodology represents an example of a post-condensation Ugi modification (Hulme & Gore, 2003) that employs two internal nucleophiles in distinct operations, generating a novel scaffold of high complexity in three succinct functional operations.
Two types of crystals were formed: very fine yellow needles together with a few slightly larger rod-shaped pale yellow crystals. The needles did not give any measurable diffraction and the rod crystals showed weak diffraction with 60 second exposure times; a resolution cutoff of 0.87Å was applied to the dataset. The identity of the needle crystals was not established.
The molecular structure of 5 is shown in Figure 2. Molecular dimensions are unexceptional. The amine hydrogen atom was located in a difference Fourier map and its presence is confirmed by participation in hydrogen bonding discussed below.
The central 7-membered heterocyclic ring adopts a conformation that is perhaps best described as a distorted boat with the H-bearing (C3 and N3) atoms lying well out of a least squares mean plane fitted through the other five atoms in the ring [r.m.s. deviation 0.075 Å; C3 deviates by 0.679 (5) Å and N3 deviates by 0.301 (4) Å]. The compound packs as a twisted chain which propagates along the b axis by means of an R 1 2 (6) motif (Bernstein et al., 1995) formed by one of the carbonyl oxygen atoms acting as bifurcated acceptor in an N-H···O and C-H···O interaction ( Figure 3).
Methyl carbonic acid (10 ml) and N-butyl isonitrile (0.237 ml, 2.252 mmol) were then added to the latter flask. The reaction was stirred at room temperature under an atmosphere of CO 2 for 16 h. The solvent was evaporated in vacuo and the crude product purified with a Biotage Isolera4 TM system (hexane/EtOAc 10-30%) to afford the Ugi product 3 (218 mg, 0.438 mmol, 39%) as a yellow oil.