Pyridyl-substituted spiro-hydantoin crystalline forms and process

A process for preparing a substituted spiro-hydantoin compound (I) of formula:

• comprising:
• contacting alkene compound (III) of formula:
• with:
• i) methylene precursor compound and
• ii) N-substituted glycine compound of formula
• to afford said substituted spiro-hydantoin compound (I) or a pharmaceutically-acceptable salt or solvate, thereof;
• wherein:
• L and K are independently O or S;
• Z is N or CR4b;
• Ar is aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
• G is a bond, —O—, —S—, —NR1, C1-3alkylene, C1-3substituted alkylene, bivalent alkoxy, thioalkyl, aminoalkyl, sulfonyl, sulfonamidyl, acyl, or alkoxycarbonyl;
• A1 is a bond, C1-2alkylene, or C2-3alkenylene;
• A2 is a bond, C1-3alkylene, C2-3alkenylene, —C1-4alkylene-NR16—, —C1-4alkylene-NR16C(═O)—, —C1-4alkylene-S—, —C1-4alkylene-SO2—, or —C1-4alkylene-O—, wherein the A2 alkylene groups are branched or straight chain, and optionally substituted alkylene;
• Q is a bond, —C(═O)—, —C(═O)NR16—, —C(═S)NR16—, —SO2—, —SO2NR16—, —CO2—, or —NR16CO2—;
• R1 is hydrogen, alkyl, or substituted alkyl;
• R2 is hydrogen, alkyl, substituted alkyl, —OR12, —NR12R13, —C(═O)R12, —CO2R12, —C(═O)NR12R13, —NR12C(═O)R13, —NR12C(═O)OR13, —S(O)pR13a, —NR12SO2R13a, —SO2NR12R13, cycloalkyl, substituted cycloalkyl, heterocyclo, substituted heterocyclo, aryl, substituted aryl, heteroaryl, or substituted heteroaryl;
• R4aR4b, and R4c are independently hydrogen, halogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, nitro, cyano, —SR14, —OR14, —NR14R15, —NR14C(═O)R15, —CO2R14, —C(═O)R14, —C(═O)NR14R15, aryl, substituted aryl, heterocyclo, substituted heterocyclo, cycloalkyl, substituted cycloalkyl, heteroaryl, and/or substituted heteroaryl;
• R12, R13, R14, and R15 are independently hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, and/or substituted heterocyclo;
• or (ii) R12 is taken together with R13, and/or R14 is taken together with R15 to form a heteroaryl or heterocyclo ring;
• R13a is alkyl, substituted alkyl, cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, or substituted heterocyclo;
• R16 is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo, cycloalkyl, or substituted cycloalkyl, provided that R16 is not hydrogen when A1, Q, and A2 are each bonds;
• R′ is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclo, substituted heterocyclo, cycloalkyl, or substituted cycloalkyl;
• and
• p is 1 or 2.