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US 2004/0171818 A1Published application
Processes for the preparation of 6-11 bicyclic erythromycin derivatives
AssigneeEnanta Pharmaceuticals, Inc.
InventorsGuoyou Xu, Datong Tang, Yonghua Gai, Heejin Kim, Guoqiang Wang, Ly Tam Phan, Yat Sun Or, Zhe Wang
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Abstract
The present invention relates to processes and intermediates for the preparation of 6-11 bicyclic erythromycin derivatives. In particular, the present invention relates to processes and intermediates for the preparation of a compound of formula (IX-c): 1
Claims61
A process comprising the step of reacting a compound of formula (I):
- 37
- or a pharmaceutically acceptable salt thereof, with a compound of formula II:
- 38
- to produce a compound of formula III:
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- wherein,
- Each R1 is independently selected from hydrogen, acyl, silane, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, saturated or unsaturated heterocyclic group;
- Each of R3 and R4 is independently selected from hydrogen, acyl, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, saturated or unsaturated heterocyclic group;
- or can be taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted heterocyclic or heteroaromatic ring;
- Q is independently selected from R1, OR1, or OC(O)R1;
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- Z is selected from R1, OR1, OC(O)R1, OC(O)NR3R4, OS(O)nR1, or
- one of J or G is hydrogen and the other is selected from R1, OR1, or NR3R4;
- or, J and G, taken together with the carbon atom to which they are attached, are selected from C═O, C═NR1, C═NOR1, C═NO(CH2)mR1, C═NNHR1, C═NNHCOR1, C═NNHCONR3R4, C═NNHS(O)nR1, or C═N—N═CHR1;
- R11 is independently selected from R1;
- Rp is independently selected from R1;
- m is an integer;
- and
- n is 0, 1, or 2.
16 more elements
A process of preparing a compound of formula (XI):
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- the process comprising the steps of:
- (a) reacting pyrazole with methyl 6-chloronicotinate in the presence of a strong base to provide 6-pyrazol-1-yl-nioctinic acid methyl ester (compound of formula (XI-a));
- (b) reducing the compound of formula (XI-a) prepared in Step (a) with a reducing agent to provide (6-pyrazol-1-yl-pyridin-3-yl)-methanol (compound of formula (XI-b));
- (c) halogenating the compound of formula (XI-b) prepared in Step (b) with a chlorinating agent to provide 5-chloromethyl-2-pyrazol-1-yl-pyridine (compound of formula (XI-c));
- (d) adding the compound of formula (XI-c), prepared in Step (c) with a compound of formula (XI-e):
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- wherein A and B are both hydrogen or taken together with the carbon atoms to which they are attached are selected from aryl, substituted aryl, heterocyclic, or substituted heterocyclic, to provide a compound of formula (XI-d):
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- and
- (e) hydrolyzing a compound of formula (XI-d), prepared in Step (d), with a base.
8 more elements
Dependencies are inferred from the claim text.