US5861532A
Expired / Lapsed
US
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Solid-phase synthesis of N-alkyl amides
Assignee: Novartis Vaccines and Diagnostics Inc
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Filing: 1997-03-04
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Granted: 1999-01-19
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Expires: 2017-03-04
Abstract
Abstract Methods for solid phase synthesis of N-alkyl amides comprise reductive amination of carbonyl compounds using a reducing agent and an amine-containing linker bound to a solid support. The methods afford high yields of linker-bound, monoalkylated amines, and subsequent coupling with acid derivatives provide derivatized N-substituted amides in excellent yields after cleavage from the solid-phase. Compositions useful in solid phase synthesis are also described.
Inventors
- 👤 Edward G. Brown
- 👤 John M. Nuss
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 16:07
CPC Classifications
C; C07; C07C; C07C231/00; C07C231/02; C07D; C07D307/00; C07D307/02; C07D307/34; C07D307/38; C07D307/52; C40; C40B; C40B40/00
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
97 words
A method for the solid phase synthesis of an N-substituted amide product, comprising: a) providing: i) a carbonyl compound, ii) a linker bound to a solid support, said solid support-bound linker comprising at least one amine group, iii) a reducing agent, and iv) an aqueous solvent system; b) reacting said amine group of said solid support-bound linker with said carbonyl compound and said reducing agent, said reaction occurring in the presence of said aqueous solvent system and yielding an N-alkylated solid support-bound linker; and c) treating said N-alkylated solid support-bound linker, thereby generating said N-substituted amide product.
Claim 2
Independent Claim
97 words
A method for the solid phase synthesis of an N-substituted amide product, comprising: a) providing: i) a carbonyl compound, ii) a linker bound to a solid support, said solid support-bound linker comprising at least one amine group, iii) a reducing agent, and iv) an aqueous solvent system; b) reacting said amine group of said solid support-bound linker with said carbonyl compound and said reducing agent, said reaction occurring in the presence of said aqueous solvent system and yielding an N-alkylated solid support-bound linker; and c) treating said N-alkylated solid support-bound linker, thereby generating said N-substituted amide product.
Claim 3
Dependent Claim
23 words
The method of claim 1, wherein said linker is selected from the group consisting of benzhydrylamine, benzhydrylamine derivatives, methylbenzhydrylamine and methylbe drylamine derivatives.
Claim 4
Dependent Claim
15 words
The method of claim 1, wherein said solid support-bound linker is 4 (2',4'-dimethoxyphenyl)-aminomethyl!-phenoxymethyl-linked polystyrene resin.
Claim 5
Dependent Claim
19 words
The method of claim 1, wherein said carbonyl compound is selected from the group consisting of aldehydes and ketones.
Claim 6
Dependent Claim
14 words
The method of claim 1, wherein said reducing agent is a hydride reducing agent.
Claim 7
Dependent Claim
13 words
The method of claim 5, wherein said hydride reducing agent is sodium cyanoborohydride.
Claim 8
Dependent Claim
35 words
The method of claim 1, wherein said aqueous solvent system comprises a compound from the group consisting of ρ-dioxane, tetrahydropyran, ethanol, methanol, isopropanol, propanol, N,N-dimethylformamide, N,N-dimethylacetamide, acetamide, N,N,N',N'-tetramethyl urea, N-methylpyrrolidinone, 2-ethoxyethanol, glyme, diglyme, and tetrahydrofuran.
Claim 9
Dependent Claim
14 words
The method of claim 1, wherein said aqueous solvent system comprises an oxidation inhibitor.
Claim 10
Dependent Claim
13 words
The method of claim 1, wherein said reacting step is a reductive alkylation.
Claim 11
Dependent Claim
29 words
The method of claim 1, wherein said treating step comprises acylating said N-alkylated solid support with a compound selected from the group consisting of acid chlorides and acid anhydrides.
Claim 12
Dependent Claim
20 words
The method of claim 1, wherein step (c) includes cleavage of the product from the support under mild cleavage conditions.
Claim 13
Dependent Claim
28 words
The method of claim 11, wherein the mild cleavage conditions comprise exposure to trifluoroacetic acid and water in dichloromethane, or a carbodiimide and an acid at room temperature.
Claim 14
Dependent Claim
22 words
The method of claim 12, wherein the acid is selected from the group consisting of bromoacetic acid, chloroacetic acid, and phenylacetic acid.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 2002-01-18 | 2002-07-20 | 2003-01-19 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2006-01-18 | 2006-07-20 | 2007-01-19 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2010-01-18 | 2010-07-20 | 2011-01-19 | $7700.00 | Window Closed / Lapsed |