Novel process for preparation of optically pure and optionally substituted 2-(1-hydroxy-alkyl)-chromen-4-one derivatives and their use in preparing pharmaceuticals

A process for preparing a compound of formula (IB)

• or a salt thereof, the process comprising
• (a) treating a compound of formula (6) with a compound of formula (B) wherein Pg is a protecting group
• to give a compound of formula (7b)
• and
• (b) deprotecting the compound formed in step (a) to obtain a compound of formula (IB) and optionally converting it to its salt,
• wherein
• each occurrence of R is independently selected from hydrogen, hydroxy, halogen, carboxyl, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, —COORx, —C(O)Rx, —C(S)Rx, —C(O)NRxRy, —C(O)ONRxRy, —NRxRy, —NRxCONRxRy, —N(Rx)SORx, —N(Rx)SO2R, —(═N—N(Rx)Ry), —NRxC(O)ORy, —NRxC(O)Ry—, —NRxC(S)Ry—NRxC(S)NRxRy, —SONRxRy, —SO2NRxRy, —ORx, —ORxC(O)NRxRy, —ORxC(O)ORx, —OC(O)Rx, —OC(O)NRxRy, —RxNRyC(O)Rz, —RxORy, —RxC(O)OR, —RxC(O)NRxRy, —RxC(O)Ry, —RxOC(O)Ry, —SRx, —SORx, —SO2Rx, and —ONO2, wherein each occurrence of Rx, Ry and Rz is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heterocyclylalkyl ring, or substituted or unsubstituted amino, or (i) any two of Rx and Ry, when bound to a common atom, are joined to form a substituted or unsubstituted, saturated or unsaturated 3-14 membered ring, which may optionally include heteroatoms which may be the same or different and are selected from O, NRz or S, or (ii) any two of Rx and Ry, when bound to a common atom, are joined to form an oxo (═O), thio (═S) or imino (═NRf) (wherein Rf is hydrogen or substituted or unsubstituted alkyl);
• R1 is substituted or unsubstituted C1-6 alkyl;
• Cy1 is a monocyclic or bicyclic group selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;
• Pg is a protecting group;
• and
• n is an integer selected from 0, 1, 2, 3 or 4.

A compound of formula (IA) or (IB)

• or a salt thereof,
• wherein
• each occurrence of R is independently selected from hydrogen, hydroxy, halogen, carboxyl, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, —COORx, —C(O)Rx, —C(S)Rx, —C(O)NRxRy, —C(O)ONRxRy, —NRxRy, —NRxCONRxRy, —N(Rx)SORx, —N(Rx)SO2R, —(═N—N(Rx)Ry), —NRxC(O)ORy, —NRxC(O)Ry—, —NRxC(S)Ry—NRxC(S)NRxRy, —SONRxRy, —SO2NRxRy, —ORx, —ORxC(O)NRxRy, —ORxC(O)ORx, —OC(O)Rx, —OC(O)NRxRy, —RxNRyC(O)RZ, —RxORy, —RxC(O)OR, —RxC(O)NRxRy, —RxC(O)Ry, —RxOC(O)Ry, —SRx, —SORx, —SO2Rx, and —ONO2, wherein each occurrence of Rx, Ry and Rz is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heterocyclylalkyl ring, or substituted or unsubstituted amino, or (i) any two of Rx and Ry, when bound to a common atom, are joined to form a substituted or unsubstituted, saturated or unsaturated 3-14 membered ring, which may optionally include heteroatoms which may be the same or different and are selected from O, NRz or S, or (ii) any two of Rx and Ry, when bound to a common atom, are joined to form an oxo (═O), thio (═S) or imino (═NRf) (wherein Rf is hydrogen or substituted or unsubstituted alkyl);
• R1 is substituted or unsubstituted C1-6 alkyl;
• Cy1 is a group selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;
• and
• n is an integer selected from 0, 1, 2, 3 or 4,
• wherein the compound is not selected from
• or a salt thereof.

A compound selected from

• (R)-6-fluoro-3-(3-fluorophenyl)-2-(1-hydroxyethyl)-4H-chromen-4-one;
• (R)-2-(1-hydroxyethyl)-5-methyl-3-phenyl-4H-chromen-4-one;
• (R)-6-fluoro-2-(1-hydroxyethyl)-3-phenyl-4H-chromen-4-one;
• (R)-2-(1-hydroxyethyl)-3-phenyl-4H-chromen-4-one;
• (R)-3-(3-fluorophenyl)-2-(1-hydroxypropyl)-4H-chromen-4-one;
• (R)-3-(3-fluorophenyl)-2-(1-hydroxyethyl)-4H-chromen-4-one;
• (S)-3-(3-fluorophenyl)-2-(1-hydroxyethyl)-4H-chromen-4-one;
• and salts thereof.