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US 2024/0239803 A1Published application
Synthesis of coelenterazine
AssigneeInternational Paper Company
InventorsRajagopala Reddy Duvvuru, Rama Bhatt, Anil Kumar
Life of this patent
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Abstract
Disclosed herein are synthesis methods for coelenterazine. Also disclosed are articles including the coelenterazine and coelenterazine derivatives. Representative absorbent articles include disposable diapers and adult incontinence products.
Claims18
A method of making coelenterazine, comprising:
- (a) reacting 3-benzylpyrazin-2-amine (25) with N-bromosuccinimide to provide 3-benzyl-5-bromopyrazin-2-amine (2);
- (b) reacting the 3-benzyl-5-bromopyrazin-2-amine (2) in two sequential steps to provide 4-(5-amino-6-benzylpyrazin-2-yl)phenol (7) (coelenteramine);
- and
- (c) coupling the 4-(5-amino-6-benzylpyrazin-2-yl)phenol (7) with silyl-protected 1,1-diethoxy-3-(4-hydroxyphenyl)propan-2-one to provide coelenterazine, or a salt thereof.
1 more element
A method of making coelenterazine, comprising:
- (a) reacting pyrazin-2-amine (24) with benzyl chloride to provide 3-benzylpyrazin-2-amine (25);
- (b) reacting 3-benzylpyrazin-2-amine (25) with N-bromosuccinimide to provide 3-benzyl-5-bromopyrazin-2-amine (2);
- (c) reacting the 3-benzyl-5-bromopyrazin-2-amine (2) in two sequential steps to provide 4-(5-amino-6-benzylpyrazin-2-yl)phenol (7) (coelenteramine);
- and
- (d) coupling the 4-(5-amino-6-benzylpyrazin-2-yl)phenol (7) with silyl-protected 1,1-dimethoxy-3-(4-hydroxyphenyl)propan-2-one or silyl-protected 1,1-diethoxy-3-(4-hydroxyphenyl)propan-2-one to provide coelenterazine, or a salt thereof.
2 more elements
A method of making 4-(5-amino-6-benzylpyrazin-2-yl)phenol (7), comprising:
- reacting 3-benzylpyrazin-2-amine (25) with N-bromosuccinimide to provide 3-benzyl-5-bromopyrazin-2-amine (2);
- reacting the 3-benzyl-5-bromopyrazin-2-amine (2) with 4-methoxyphenyl boronic acid (4) in the presence of a palladium catalyst to provide 3-benzyl-5-(4-methoxyphenyl)pyrazin-2-amine (5);
- and
- deprotecting the 3-benzyl-5-(4-methoxyphenyl)pyrazin-2-amine (5) to provide the 4-(5-amino-6-benzylpyrazin-2-yl)phenol (7) (coelenteramine).
1 more element
A method of making 3-(4-((tert-butyldimethylsilyl)oxy)phenyl)-1,1-diethoxypropan-2-one (23) or 3-(4-((tert-butyldimethylsilyl)oxy)phenyl)-1,1-dimethoxypropan-2-one (27), comprising:
- reacting 4-hydroxybenzaldehyde (8) with tert-butyldimethylsilyl chloride to provide 4-((tert-butyldimethylsilyl)oxy)benzaldehyde;
- reacting the 4-((tert-butyldimethylsilyl)oxy)benzaldehyde with sodium borohydride to provide (4-((tert-butyldimethylsilyl)oxy)phenyl)methanol;
- reacting the (4-((tert-butyldimethylsilyl)oxy)phenyl)methanol with methanesulfonyl chloride to provide tert-butyl(4-(chloromethyl)phenoxy)dimethylsilane (21);
- reacting the tert-butyl(4-(chloromethyl)phenoxy)dimethylsilane (21) with magnesium to provide (4-((tert-butyldimethylsilyl)oxy)benzyl)magnesium chloride;
- and
- reacting the (4-((tert-butyldimethylsilyl)oxy)benzyl)magnesium chloride with ethyl 2,2-diethoxyacetate or with methyl 2,2-dimethoxyacetate to provide the 3-(4-((tert-butyldimethylsilyl)oxy)phenyl)-1,1-diethoxypropan-2-one (23) or 3-(4-((tert-butyldimethylsilyl)oxy)phenyl)-1,1-dimethoxypropan-2-one (27), respectively,
- wherein the 3-(4-((tert-butyldimethylsilyl)oxy)phenyl)-1,1-diethoxypropan-2-one (23) is further purified by chromatography with an eluant comprising triethylamine.
4 more elements
A method of making 1,1-diethoxy-3-(4-hydroxyphenyl)propan-2-one (14), comprising:
- reacting 4-hydroxybenzaldehyde with benzyl chloride to provide 4-(benzyloxy)benzaldehyde;
- reacting the 4-(benzyloxy)benzaldehyde with sodium borohydride to provide (4-(benzyloxy)phenyl)methanol;
- reacting (4-(benzyloxy)phenyl)methanol with SOCl2 or methane sulfonyl chloride to provide 1-(benzyloxy)-4-(chloromethyl)benzene;
- reacting 1-(benzyloxy)-4-(chloromethyl)benzene with ethyl 2,2-diethoxyacetate and magnesium to provide 3-(4-(benzyloxyl)phenyl)-1,1-diethoxypropan-2-one;
- and
- reprotecting the 3-(4-(benzyloxyl)phenyl)-1,1-diethoxypropan-2-one with hydrogen and palladium over carbon to provide 1,1-diethoxy-3-(4-hydroxyphenyl)propan-2-one (14).
3 more elements
Dependencies are inferred from the claim text.