US 12,612,415 B2 · Stereoselective process for preparing substituted polycyclic pyridone

Abstract

The present invention provides industrially suitable processes for preparing intermediates in the production of substituted polycyclic pyridone derivatives having a cap-dependent endonuclease inhibitory activity. In the process as shown below, wherein each symbol is as defined in the specification, an optically active substituted tricyclic pyridone derivative of the formula (VII) is obtained in high yield and high enantioselectivity by subjecting a compound of the formula (III) or (VI) to intramolecular cyclization with controlling stereochemistry to obtain a compound of the formula (IV) having a removable functional group on an asymmetric carbon, and then removing the functional group thereof;

Claims2

Dependent claims

A process for preparing a compound of the formula (III), or a salt thereof:

wherein R1, R7, R8, RA1, RA2, RA3 and X are each as defined below;
the process comprising reacting a compound of the formula (Ia):
wherein R1 is hydrogen or a protecting group for hydroxyl group;
R7 is NH2 or NHR2;
R2 is a protecting group for amino group;
with a compound of the formula (II):
wherein RA1 is hydrogen or RA;
RA2 is hydrogen or RA;
RA3 is hydrogen or RA;
X is O, CH2 or CHRA;
RA is an optionally protected carboxy group;
provided that one of RA1, RA2 and RA3 is RA, the other two are hydrogen, and X is O or CH2, or RA1, RA2 and RA3 are hydrogen and X is CHRA;
R8 is —CHO or —CH(OR4)(OR4);
R4 is each independently hydrogen or a protecting group deprotectable by an acid, or two R4 may be taken together to form a ring.

11 more elements

Dependencies are inferred from the claim text.

Facts

Application

17/679,449Filed 24 Feb 2022 · division

Priority

JP 2017-1958026 Oct 2017

Published

US 2023/0040262 A19 Feb 2023

Granted

28 Apr 2026

Term ends

Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07D 498/14
In which the condensed system contains three hetero rings: ortho-condensed systems
C07C 215/10
And acyclic: with one amino group and at least two hydroxy groups bound to the carbon skeleton
C07C 217/08
Having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted: the oxygen atom of…
C07D 213/89
Having three double bonds between ring members or between ring members and non-ring members: with hetero atoms directly attached to the ring…

Family

PCT/JP2018/037390Parent of this division · filed 5 Oct 2018

US 2023/0040262 A1Pre-grant publication · published 9 Feb 2023

Application16/652,122Parent of this division

US 11,286,262 B2Parent of this division

US 2020/0247818 A1Published application

US 12,612,415 B2This patent

From the US filing history. Foreign family members aren’t listed.

Stereoselective process for preparing substituted polycyclic pyridone

Life of this patent

Stereoselective process for preparing substituted polycyclic pyridone

Life of this patent

Abstract

Claims2