32326-25-3

Basic information

• Product Name: 3-Amino-5-methoxyisoxazole
• Synonyms: 3-Amino-5-methoxyisoxazole;5-methoxyisoxazol-3-amine;3-AMINE-5-METHOXYISOXAZOLE;3-Amino-5-methoxisoxazole;5-Methoxy-1,2-oxazol-3-aMine;5-Methoxy-isoxazol-3-ylamine
• CAS NO: 32326-25-3
• Molecular Formula: C₄H₆N₂O₂
• Molecular Weight: 114.10264
• Mol File: 32326-25-3.mol

Chemical Properties

• Boiling Point: 282°C
• Flash Point: 124°C
• Appearance: /
• Density: 1.243
• Storage Temp.: 2-8°C(protect from light)
• PKA: 1.85±0.10(Predicted)
• CAS DataBase Reference: 3-Amino-5-methoxyisoxazole(CAS DataBase Reference)
• NIST Chemistry Reference: 3-Amino-5-methoxyisoxazole(32326-25-3)
• EPA Substance Registry System: 3-Amino-5-methoxyisoxazole(32326-25-3)

Safety Data

• Hazardous Substances Data: 32326-25-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
3-Amino-5-methoxyisoxazole is used as a key reactant in the synthesis of pyrazolidine derivatives and 1-substituted tetrazoles. These compounds are of significant interest in the pharmaceutical industry due to their diverse range of biological activities, including antimicrobial, antiviral, and anticancer properties. The cyclization of amines with 3-amino-5-methoxyisoxazole allows for the development of novel therapeutic agents with improved pharmacological profiles.
Used in Organic Synthesis:
3-Amino-5-methoxyisoxazole is also used as a building block in the synthesis of various organic compounds, such as heterocycles, natural products, and pharmaceuticals. Its unique structure and reactivity make it a valuable component in the design and synthesis of complex organic molecules with potential applications in various fields, including materials science, agrochemistry, and medicinal chemistry.

Synthetic route

1-cyano-2,2-bis(methoxy)ethylene (15732-02-2) → 3-amino-5-methoxyisoxazole (32326-25-3)

Conditions	Yield
With sodium hydroxide; hydroxylamine hydrochloride In methanol at 45 - 60℃; for 7h;	75%
With sodium hydroxide; hydroxylamine hydrochloride In methanol; water	70.6%

orthoformic acid triethyl ester (122-51-0) + 3-amino-5-methoxyisoxazole (32326-25-3) → 5-methoxy-3-(1H-tetrazol-1-yl)isoxazole

Conditions	Yield
With sodium azide In neat (no solvent) at 90℃; for 0.666667h; Reagent/catalyst; Green chemistry;	91%

C20H20F3NO4S + 3-amino-5-methoxyisoxazole (32326-25-3) → 1-(2-(5-methoxyisoxazol-3-yl-amino)ethyl)-7-(trifluoromethyl)-3,4-dihydro-1H-benzo[b]azepin-5(2H)-one

Conditions	Yield
With potassium hydrogencarbonate In methanol for 8h; Reflux;	88%

potassium thioacyanate (333-20-0) + methyl chloroformate (79-22-1) + 3-amino-5-methoxyisoxazole (32326-25-3) → (5-methoxycarbonylamino-[1,2,4]thiadiazol-3-yl)-acetic acid methyl ester (149196-71-4)

Conditions	Yield
In acetonitrile 1.) 70 deg C, 30 min; 2.) 5 deg C, 10 min then 20 deg C, 15 min;	86%
1.) MeCN, 70 deg C, 30 min, 2.) MeCN, a) 5 deg C, 10 min, b) RT, 15 min; Yield given. Multistep reaction;

potassium thioacyanate (333-20-0) + chloroformic acid ethyl ester (541-41-3) + 3-amino-5-methoxyisoxazole (32326-25-3) → methyl 2-(5-ethoxycarbonylamino-1,2,4-thiadiazol-3-yl)acetate (150215-07-9)

Conditions	Yield
In acetonitrile 1.) 70 deg C, 30 min; 2.) 5 deg C, 10 min then 20 deg C, 15 min;	83%
1.) MeCN, 70 deg C, 30 min, 2.) MeCN, a) 5 deg C, 10 min, b) RT, 15 min; Yield given. Multistep reaction;

methyl chloroformate (79-22-1) + 3-amino-5-methoxyisoxazole (32326-25-3) → (5-methoxycarbonylamino-[1,2,4]thiadiazol-3-yl)-acetic acid methyl ester (149196-71-4)

Conditions	Yield
In acetonitrile	80.6%

chloroformic acid ethyl ester (541-41-3) + 3-amino-5-methoxyisoxazole (32326-25-3) → methyl 2-(5-ethoxycarbonylamino-1,2,4-thiadiazol-3-yl)acetate (150215-07-9)

Conditions	Yield
In acetonitrile	78.9%

potassium thioacyanate (333-20-0) + phenyl chloroformate (1885-14-9) + 3-amino-5-methoxyisoxazole (32326-25-3) → methyl 2-(5-phenoxycarbonylamino-1,2,4-thiadiazol-3-yl)acetate (150215-08-0)

Conditions	Yield
In acetonitrile 1.) 70 deg C, 30 min; 2.) 5 deg C, 10 min then 20 deg C, 15 min;	60%
1.) MeCN, 70 deg C, 30 min, 2.) MeCN, a) 5 deg C, 10 min, b) RT, 15 min; Yield given. Multistep reaction;

Benzoyl isothiocyanate (532-55-8) + 3-amino-5-methoxyisoxazole (32326-25-3) → methyl 2-(5-phenylcarbonylamino-1,2,4-thiadiazol-3-yl)acetate

Conditions	Yield
In tetrahydrofuran; ethanol	57.7%

phenyl chloroformate (1885-14-9) + 3-amino-5-methoxyisoxazole (32326-25-3) → methyl 2-(5-phenoxycarbonylamino-1,2,4-thiadiazol-3-yl)acetate (150215-08-0)

Conditions	Yield
In acetonitrile	57.4%

potassium thioacyanate (333-20-0) + benzyl chloroformate (501-53-1) + 3-amino-5-methoxyisoxazole (32326-25-3) → methyl 2-(5-benzyloxycarbonylamino-1,2,4-thiadiazol-3-yl)acetate (150215-09-1)

Conditions	Yield
In acetonitrile 1.) 70 deg C, 30 min; 2.) 5 deg C, 10 min then 20 deg C, 15 min;	40%
1.) MeCN, 70 deg C, 30 min, 2.) MeCN, a) 5 deg C, 10 min, b) RT, 15 min; Yield given. Multistep reaction;

benzyl chloroformate (501-53-1) + 3-amino-5-methoxyisoxazole (32326-25-3) → methyl 2-(5-benzyloxycarbonylamino-1,2,4-thiadiazol-3-yl)acetate (150215-09-1)

Conditions	Yield
In acetonitrile	24.9%

[2-methyl-1-(pyrazolidine-1-carbonyl)-butyl]-carbamic acid tert-butyl ester + phosgene (75-44-5) + 3-amino-5-methoxyisoxazole (32326-25-3) → {1-[2-(5-methoxy-isoxazol-3-ylcarbamoyl)-pyrazolidine-1-carbonyl]-2-methyl-butyl}-carbamic acid tert-butyl ester

Conditions	Yield
With pyridine In dichloromethane; toluene at 20℃;

methyl chloroformate (79-22-1) + 3-amino-5-methoxyisoxazole (32326-25-3) → [5-Amino-3-(1,2,4-thiadiazole)]acetic acid, methyl ester

Conditions	Yield
In tetrahydrofuran; water

Upstream product

• 15732-02-2 1-cyano-2,2-bis(methoxy)ethylene 

Downstream Products

• 150215-07-9 methyl 2-(5-ethoxycarbonylamino-1,2,4-thiadiazol-3-yl)acetate 
• 150215-08-0 methyl 2-(5-phenoxycarbonylamino-1,2,4-thiadiazol-3-yl)acetate 
• 150215-09-1 methyl 2-(5-benzyloxycarbonylamino-1,2,4-thiadiazol-3-yl)acetate 

Relevant articles and documents

Process for preparing 1,2,4-thiadiazole derivatives

An improved process for the production of 5-amino-1,2,4-thiadiazol-3-yl-(2-(lower)-alkoxyimino)acetic acids starting from 5-substituted- or unsubstituted-3-amino-isoxazole compounds is disclosed herein. The title compounds are useful as acylating agents for the production of 7-acylaminocephalosporins.

Practical preparation of (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetic acid: A side-chain of the fourth generation of cephem antibiotics

A Z-isomer (4) of 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetic acid, which is the common acyl moiety of clinically useful cephem antibiotics, has been prepared from the aminoisoxazoles through the skeletal rearrangement in several routes. Reaction of 3-amino-5-methoxyisoxazole (7) with alkoxycarbonyl isothiocyanates gave methyl 2-(5-alkoxycarbonylamino-1,2,4-thiadiazol-3-yl)acetates (8), which were converted into the target compound 4 through the reaction of the corresponding keto ester with O-methylhydroxylamime. Compound 4 was prepared similarly from 3-aminoisoxazole (10). Also, O-methylation of 2-hydroxyimino-2-(5-methoxycarbonylamino-1,2,4-thiazol-3-yl)acetate (15) with methyl iodide or dimethyl sulfate in the presence of barium oxide and barium hydroxide octahydrate was found to afford exclusively the desired Z-isomer (14a) of methyl 2-(5-methoxycarbonylamino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)aceta te, which was led to 4.