Intermediate for preparing eribulin mesylate and process for preparing the same
AssigneeYonsung Fine Chemical Co., Ltd.
InventorsHyoseon LEE, Hyunik SHIN, Keeyoung LEE, Changyoung OH
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Abstract
The present invention relates to a process for preparing an intermediate for the preparation of eribulin mesylate with high yields, and an intermediate therefor.
Claims20
A process for preparing a compound of the following formula (3), which comprises the steps of:
- (i) subjecting a compound of the following formula (4) to Wittig reaction to obtain a compound of the following formula (5);
- (ii) selectively deprotecting a PG2 group of the compound of the following formula (5) to obtain a compound of the following formula (6);
- (iii) subjecting the compound of the following formula (6) to cyclization to obtain a compound of the following formula (7);
- (iv) subjecting the compound of the following formula (7) to hydrogenation to obtain a compound of the following formula (8);
- and
- (v) reducing an ester group of the compound of the following formula (8):
- wherein,
- PG1 represents a diol protecting group forming a 5-membered heterocycle by combining each other,
- PG2 represents a silyl protecting group, and
- R1 represents hydrogen or a C1-C6 alkyl group.
A compound of the following formula (3):
- wherein,
- PG1 represents a diol protecting group forming a 5-membered heterocycle by combining each other.
A compound of the following formula (7):
- wherein,
- PG1 represents a diol protecting group forming a 5-membered heterocycle by combining each other, and
- R1 represents hydrogen or a C1-C6 alkyl group.
A process for preparing a compound of the following formula (7), which comprises the steps of:
- (i) subjecting a compound of the following formula (4) to Wittig reaction to obtain a compound of the following formula 5):
- (ii) selectively deprotecting a PG2 group of the compound of the following formula (5) to obtain a compound of the following formula (6);
- and
- (iii) subjecting the compound of the following formula (6) to cyclization:
- wherein,
- PG1 represents a diol protecting group forming a 5-membered heterocycle by combining each other,
- PG2 represents a silyl protecting group, and
- R1 represents hydrogen or a C1-C6 alkyl group.
A process for preparing a compound of the following formula (2), which comprises the steps of:
- (vi) subjecting a compound of the following formula (3) to Horner-Wadsworth-Emmons reaction to obtain a compound of the following formula (9);
- (vii) selectively deprotecting a primary hydroxyl protecting group of the compound of the following formula (9) to obtain a compound of the following formula (10);
- (viii) oxidizing the compound of the following formula (10) to obtain a compound of the following formula (11);
- (ix) subjecting the compound of the following formula (11) to Nozaki-Hiyama-Kishi reaction with (2-bromovinyl)trimethylsilane to obtain a compound of the following formula (12);
- (x) deprotecting a secondary hydroxyl protecting group of the compound of the following formula (12) to obtain a compound of the following formula (13);
- (xi) protecting a hydroxyl group of the compound of the following formula (13) to obtain a compound of the following formula (14);
- (xii) subjecting a trimethylsilyl group of the compound of the following formula (14) to substitution with an iodide to obtain a compound of the following formula (15);
- and
- (xiii) reducing an ester group of the compound of the following formula (15):
- wherein,
- PG1 represents a diol protecting group forming a 5-membered heterocycle by combining each other,
- TMS represents trimethylsilyl, and
- TBS represents t-butyldimethylsilyl.
The process according to claim wherein the oxidation of step (viii) is carried out using sodium periodate.
Dependencies are inferred from the claim text.