# US 10,308,672 B2 · Method for producing monomer for single-stranded nucleic acid molecule

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- Number: US 10,308,672 B2
- Document ID: US10308672B2
- Status: Granted
- Kind: B2
- Application number: 16/085,330
- Filed: 2017-04-17
- Published: 2019-04-04
- Granted: 2019-06-04
- Earliest claimed: 2016-04-26
- Assignees: Sumitomo Chemical Company, Limited
- Applicants: Sumitomo Chemical Company, Limited
- Inventors: Kanako Sato; Hideki Ihara
- Web page: https://patentgrep.com/patent/US10308672B2

## CPC

- C07F 9/572: Five-membered rings
- C12N 15/113: Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)}
- C12N 2330/30: chemically synthesised
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

A compound represented by formula (3): or an enantiomer thereof can be obtained by comprising: reacting a compound represented by formula (1): or an enantiomer thereof with 6-hydroxyhexanoic acid in a solvent in the presence of an additive such as 1-hydroxybenzotriazole and a condensing agent, and then mixing the resultant reaction mixture, water, and a base such as alkali metal hydroxide to produce a compound represented by formula (2): or an enantiomer thereof; and reacting the compound represented by formula (2) or an enantiomer thereof with 2-cyanoethyl-N,N,N′,N′-tetraisopropylphosphorodiamidite in a solvent in the presence of a coupling activator.

## Claims

### Claim 1

A method for producing a compound represented by formula (3):
or an enantiomer thereof, comprising:
reacting a compound represented by formula (1):
or an enantiomer thereof with 6-hydroxyhexanoic acid in a solvent in the presence of an additive and a condensing agent selected from the group consisting of 1-hydroxybenzotriazole, 1-hydroxy-7-azabenzotriazole, N-hydroxysuccinimide, ethyl(hydroxyimino)cyanoacetate, N,N′-disuccinimidyl carbonate, N-hydroxyphthalimide, N-hydroxypiperidine, 3-hydroxy-4-oxo-3,4-dihydro-1,2,3-benzotriazine and N-hydroxy-5-norbornene-2,3-dicarboxylic acid imide, and then mixing the resultant reaction mixture, water, and a base selected from the group consisting of alkali metal hydroxide, alkali metal carbonate, a bicyclic amidine compound, alkali metal alkoxide, and quaternary ammonium hydroxide to produce a compound represented by formula (2):
or an enantiomer thereof; and
reacting the compound represented by formula (2) and obtained in the production step or an enantiomer thereof with 2-cyanoethyl-N,N,N′,N′-tetraisopropylphosphorodiamidite in a solvent in the presence of a coupling activator to obtain the compound represented by formula (3) or an enantiomer thereof.

### Claim 2 (depends on 1)

The production method according to claim 1, wherein the base is an alkali metal hydroxide.

### Claim 3 (depends on 1)

The production method according to claim 1, wherein the condensing agent is 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, N,N′-dicyclohexylcarbodiimide, N,N′-diisopropylcarbodiimide, 1,1-carbonyldiimidazole, 1-propylphosphonic anhydride cyclic trimer or 2-chloro-4,6-dimethoxy-1,3,5-triazine.

### Claim 4 (depends on 1)

The production method according to claim 1, wherein the additive is 1-hydroxybenzotriazole, 1-hydroxy-7-azabenzotriazole, N-hydroxysuccinimide, ethyl (hydroxyimino)cyanoacetate or N,N′-disuccinimidyl carbonate.

### Claim 5 (depends on 1)

The production method according to claim 1, wherein the coupling activator is diisopropylaminetetrazole salt, 1H-tetrazole, 5-(ethylthio)-1H-tetrazole, 5-(benzylthio)-1H-tetrazole or 4,5-dicyanoimidazole.