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US 9,309,216 B2Granted
Process for preparation of optically pure and optionally substituted 2-(1-hydroxy-alkyl)-chromen-4-one derivatives and their use in preparing pharmaceuticals
AssigneeRhizen Pharmaceuticals SA
InventorsJayaraman V. Raman, Swaroop K. Vakkalanka
Life of this patent
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Abstract
The present invention relates to compounds useful as pharmaceutical intermediates, to processes for preparing the intermediates, to intermediates used in the processes, and to the use of the intermediates in the preparation of pharmaceuticals. In particular, the present invention concerns enantiomerically pure optionally substituted 2-(1-hydroxy-alkyl)-chromen-4-one derivatives represented by formula (IA) and (IB), processes for preparing the alcohol derivatives and their use in preparing pharmaceuticals.
Claims8
A process for preparing a compound of formula (IA)
- or a salt thereof, the process comprising
- (a) reacting a compound of formula (6) with a compound of formula (A)
- to obtain a compound of formula (7a)
- and
- (b) deprotecting the compound formed in step (a) to obtain a compound of formula (IA);
- and
- (c) optionally converting the compound of formula (IA) to 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)SO2Ry, —(═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)ORy, —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.
11 more elements
A process for preparing a compound of formula (IB)
- or a salt thereof, the process comprising
- (a) reacting a compound of formula (6) with a compound of formula (B)
- to obtain a compound of formula (7b)
- (b) deprotecting the compound formed in step (a) to obtain a compound of formula (IB);
- and
- (c) optionally converting the compound of formula (IB) to 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)SO2Ry, —(═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)ORy, —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 0, 1, 2, 3 or 4.
10 more elements
Dependencies are inferred from the claim text.