Metformin hydrochloride

Iupac Name：3-(diaminomethylidene)-1,1-dimethylguanidine;hydrochloride

Molecular Weight：165.62458

Modify Date.: 2022-11-25 02:17

Introduction:

Metformin (hydrochloride) is an FDA approved first-line drug for the treatment of type 2 diabetes. Metformin decreases hepatic glucose production, mostly through a mild and transient inhibition of the mitochondrial respiratory-chain complex 1.

View more+

Request For Quotation

1. Names and Identifiers

1.1 Name: Metformin hydrochloride
1.2 Synonyms: 1,1-Dimethylbiguanide hydrochloride 1,1-Dimethylbiguanide hydrochloride,Metformin 1,1-dimethyl-biguanidhydrochloride 3-(diaminomethylidene)-1,1-dimethylguanidine,hydrochloride diabefagos DIABETOSAN DIABEX diformin dimethylbiguanidehydrochloride Dimethyldiguanidinehydrochloride EINECS 214-230-6 GLUCOPHAGE Imidodicarbonimidic diamide, N,N-dimethyl-, hydrochloride (1:1) Metformin (hydrochloride) Metformin HCl MFCD00012582 N,N-Dimethylimidodicarbonimidic diamide hydrochloride (1:1) N1,N1-Dimethylbiguanide hydrochloride

1.3 CAS No.: 1115-70-4

1.4 CID: 14219

1.5 EINECS(EC#): 214-230-6

1.6 Molecular Formula: C4H12ClN5 (isomer)

1.7 Inchi: InChI=1S/C4H11N5.ClH/c1-9(2)4(7)8-3(5)6;/h1-2H3,(H5,5,6,7,8);1H

1.8 InChkey: OETHQSJEHLVLGH-UHFFFAOYSA-N

1.9 Canonical Smiles: CN(C)C(=N)N=C(N)N.Cl

1.10 Isomers Smiles: CN(C)C(=N)N=C(N)N.Cl

2. Properties

2.1 Melting point: 223-226℃

2.1 Boiling point: 224.1 °C at 760 mmHg

2.1 Flash Point: 89.3 °C

2.1 Precise Quality: 165.07800

2.1 PSA: 88.99000

2.1 logP: 1.05850

2.1 Λmax: 233nm(H2O)(lit.)

2.2 Appearance: crystalline solid

2.3 Storage: Keep Cold.

2.4 Color/Form: Powder

2.5 Decomposition: Hazardous decomposition products formed under fire conditions - Carbon oxides, nitrogen oxides (NOx), hydrogen chloride gas. /Metformin hydrochloride/

2.6 Water Solubility: In water, 1.06X10+6 mg/L (miscible) at 25 deg C (est)

2.7 Stability: Stable under recommended storage conditions. /Metformin hydrochloride/

2.8 StorageTemp: Store at RT

3. Use and Manufacturing

3.1 Definition: ChEBI: A hydrochloride resulting from the reaction of metformin with one molar equivalent of hydrogen chloride.

3.2 Methods of Manufacturing: 500mg of metformin free base was dissolved in 3Om^ of acetone, and then 280^ of concentrated hydrochloric acid was added, and stirred for 2 hours at room temperature. The resulting crystal was filtered and washed with acetone, and then Was charged into a 300 L autoclave100kg of dicyandiamide and 120kg of dimethylamine hydrochloride were added, and 300kg of cyclohexanol was added. The stirring speed was 45r / min, the vacuum degree of the reaction kettle was adjusted to 0.08MPa, heated to 140 and reacted for 3h. And the crude product is recrystallized with ethanol, filtered and dried to obtain metformin hydrochloride.1, 000 Kg of diphenyl ether was charged into the reaction tank, and 250 kg of dimethylamine hydrochloride and 240 kg of dicyandiamide were uniformly added thereto while stirring.After the feeding is completed, the temperature of the reaction tank is raised to 195-200°C, and the temperature is maintained for 1 hour. Insulation is completed, slowly cooled to about 50 °C and filtered, washed twice with isoamyl alcohol 250Kg at 100 °C, and dried at 130-135 °C.The crude product was recrystallized with 95percent ethanol, the amount of ethanol was about 3 times that of the crude product, and the mixture was stirred and heated to reflux so that the crude product was completely dissolved, naturally cooled to room temperature, and allowed to stand for 5 hours.White needle-like crystals were precipitated, filtered, and dried at 100°C for 12 hours to obtain 418.7 kg of metformin hydrochloride, a purity of 99.79percent, and a dicyandiamide content of less than 0.005percent (a Pharmacopoeia limit of ≤ 0.04).1 Kg of 2-cyanoguanidine and 1.15 Kg of Dimethyl amine hydrochloride were added to 2 Kg of n-butanol in a 5 L glass flask. The flask was equipped withcooling water condenser and the flask was allowed to reflux for 22 h. The resulting reaction mass was cooled to ambient temperature, preferably 10-110°C and filtered. Dried the obtained solid at 50°75°C, to get Pure Metformin hydrochloride (1.9 Kg)

3.3 Usage: An oral hypoglycemic agent

4. Safety and Handling

4.1 Symbol: GHS07

4.1 Hazard Codes: Xn

4.1 Signal Word: Warning

4.1 Risk Statements: R22;R36/38

4.1 Safety Statements: S26;S36

4.1 Exposure Standards and Regulations: The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl metformin hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Metformin hydrochloride/

4.2 Hazard Declaration: H302-H315-H319

4.2 DisposalMethods: SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

4.3 RIDADR: UN1230 - class 3 - PG 2 - Methanol, solution

4.3 Caution Statement: P305 + P351 + P338

4.3 Formulations/Preparations: Metformin hydrochloride is sold as 500- and 850-mg oral tablets (Glucophage) in the United Kingdom, Canada, Australia, South Africa, and Europe.
Diabetosan; Diabex; Glucophage; Metiguanide

4.4 WGK Germany: 3

4.4 RTECS: DU1800000

4.4 Safety: Hazard Codes:?Xn
Risk Statements: 22-36/38
R22:Harmful if swallowed.?
R36/38:Irritating to eyes and skin.
Safety Statements: 26-36
S26: In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.?
S36:Wear suitable protective clothing.
WGK Germany: 3
RTECS: DU1800000

4.5 Specification: ? Metformin hydrochloride , with CAS number of 1115-70-4, can be called 1,1-Dimethyl-biguanidhydrochloride ; Diabefagos ; Diformin ; Dimethylbiguanidehydrochloride ; Dimethyldiguanidinehydrochloride . Metformin hydrochloride (CAS NO.1115-70-4) is an oral hypoglycemic agent.

4.6 Toxicity

Organism	Test Type	Route	Reported Dose (Normalized Dose)	Effect	Source
guinea pig	LD50	intramuscular	200mg/kg (200mg/kg)	?	Toxicology and Applied Pharmacology. Vol. 2, Pg. 474, 1960.
guinea pig	LD50	intraperitoneal	200mg/kg (200mg/kg)	?	Toxicology and Applied Pharmacology. Vol. 2, Pg. 474, 1960.
guinea pig	LD50	oral	500mg/kg (500mg/kg)	?	Drugs in Japan Vol. -, Pg. 1193, 1990.
guinea pig	LD50	subcutaneous	150mg/kg (150mg/kg)	?	Drugs in Japan Vol. -, Pg. 1193, 1990.
mouse	LD50	intraperitoneal	420mg/kg (420mg/kg)	?	Drugs in Japan Vol. 6, Pg. 841, 1982.
mouse	LD50	intravenous	180mg/kg (180mg/kg)	?	U.S. Army Armament Research & Development Command, Chemical Systems Laboratory, NIOSH Exchange Chemicals. Vol. NX#04012,
mouse	LD50	oral	1450mg/kg (1450mg/kg)	?	Drugs in Japan Vol. 6, Pg. 841, 1982.
mouse	LD50	subcutaneous	225mg/kg (225mg/kg)	?	Drugs in Japan Vol. -, Pg. 1193, 1990.
rabbit	LD50	oral	350mg/kg (350mg/kg)	?	Drugs in Japan Vol. -, Pg. 1193, 1990.
rabbit	LD50	subcutaneous	150mg/kg (150mg/kg)	?	Drugs in Japan Vol. -, Pg. 1193, 1990.
rat	LD50	intraperitoneal	500mg/kg (500mg/kg)	?	French Demande Patent Document. Vol. #2220256,
rat	LD50	oral	1gm/kg (1000mg/kg)	?	"Merck Index; an Encyclopedia of Chemicals, Drugs, and Biologicals", 11th ed., Rahway, NJ 07065, Merck & Co., Inc. 1989Vol. 11, Pg. 934, 1989.
rat	LD50	subcutaneous	300mg/kg (300mg/kg)	?	"Merck Index; an Encyclopedia of Chemicals, Drugs, and Biologicals", 11th ed., Rahway, NJ 07065, Merck & Co., Inc. 1989Vol. 11, Pg. 934, 1989.

View all

5. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Acute toxicity - Oral, Category 4

Hazardous to the aquatic environment, long-term (Chronic) - Category Chronic 3

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word	Warning
Hazard statement(s)	H302 Harmful if swallowed H412 Harmful to aquatic life with long lasting effects
Precautionary statement(s)
Prevention	P264 Wash ... thoroughly after handling. P270 Do not eat, drink or smoke when using this product. P273 Avoid release to the environment.
Response	P301+P312 IF SWALLOWED: Call a POISON CENTER/doctor/\u2026if you feel unwell. P330 Rinse mouth.
Storage	none
Disposal	P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

6. NMR Spectrum

7. Synthesis Route

1115-70-4Total: 3 Synthesis Route

657-24-9 148 Suppliers

1115-70-4 363 Suppliers

Literatures:
HANALL PHARMACEUTICAL COMPANY. LTD Patent: WO2008/93984 A1, 2008 ; Location in patent: Page/Page column 29 ;
Yield: ~77%

506-59-2 236 Suppliers

127099-85-8

1115-70-4 363 Suppliers

Literatures:
Kelarev, V. I.; Bellul', M.; Zav'yalov, V. I.; Ammar Dibi; Golovin, A. N.; et al. Journal of Organic Chemistry USSR (English Translation), 1988 , vol. 24, # 5 p. 994 - 998 Zhurnal Organicheskoi Khimii, 1988 , vol. 24, # 5 p. 1100 - 1105
Yield: ~94%

124-40-3 94 Suppliers

127099-85-8

1115-70-4 363 Suppliers

Literatures:
Pharmaceutical Chemistry Journal, , vol. 21, # 12 p. 892 - 894 Khimiko-Farmatsevticheskii Zhurnal, , vol. 21, # 12 p. 1517 - 1518
Yield: null

8. Precursor and Product

precursor:

124-40-3

657-24-9

506-59-2

127099-85-8

product :

103261-85-4

657-24-9

21320-37-6

66740-79-2

9. Other Information

9.0 Usage: 1,1-Dimethylbiguanide hydrochloride is used as an antidiabetic agent, used in polycystic ovary syndrome, non-alcoholic fatty liver disease and diabetes mellitus type 2. It may also reduce weight gain in people taking atypical antipsychotics, used in a study to investigate its role in enhancing the secretions of plasma active glucagon-like peptide-1 (GLP-1) levels.

9.1 Storage Conditions: 500mg of metformin free base was dissolved in 3Om^ of acetone, and then 280^ of concentrated hydrochloric acid was added, and stirred for 2 hours at room temperature. The resulting crystal was filtered and washed with acetone, and then Was charged into a 300 L autoclave100kg of dicyandiamide and 120kg of dimethylamine hydrochloride were added, and 300kg of cyclohexanol was added. The stirring speed was 45r / min, the vacuum degree of the reaction kettle was adjusted to 0.08MPa, heated to 140 and reacted for 3h. And the crude product is recrystallized with ethanol, filtered and dried to obtain metformin hydrochloride.1, 000 Kg of diphenyl ether was charged into the reaction tank, and 250 kg of dimethylamine hydrochloride and 240 kg of dicyandiamide were uniformly added thereto while stirring.After the feeding is completed, the temperature of the reaction tank is raised to 195-200°C, and the temperature is maintained for 1 hour. Insulation is completed, slowly cooled to about 50 °C and filtered, washed twice with isoamyl alcohol 250Kg at 100 °C, and dried at 130-135 °C.The crude product was recrystallized with 95percent ethanol, the amount of ethanol was about 3 times that of the crude product, and the mixture was stirred and heated to reflux so that the crude product was completely dissolved, naturally cooled to room temperature, and allowed to stand for 5 hours.White needle-like crystals were precipitated, filtered, and dried at 100°C for 12 hours to obtain 418.7 kg of metformin hydrochloride, a purity of 99.79percent, and a dicyandiamide content of less than 0.005percent (a Pharmacopoeia limit of ≤ 0.04).1 Kg of 2-cyanoguanidine and 1.15 Kg of Dimethyl amine hydrochloride were added to 2 Kg of n-butanol in a 5 L glass flask. The flask was equipped withcooling water condenser and the flask was allowed to reflux for 22 h. The resulting reaction mass was cooled to ambient temperature, preferably 10-110°C and filtered. Dried the obtained solid at 50°75°C, to get Pure Metformin hydrochloride (1.9 Kg)

9.2 Merck: 14,5938

9.3 Adverse effects and precautions: Biguanide oral hypoglycemic agents can increase glucose utilization of surrounding tissues and inhibit the intestinal absorption of glucose, and inhibit glycogen gluconeogenesis and hepatic glucose output,it is mainly applied to obesity, dyslipidemia, type II diabetes patients. It almost has no hypoglycemic effect for normal persons , 2 to 3 hours after taking for diabetes patients ,glucose decreases significantly.
Commonly used oral hypoglycemic agents include phenformin and metformin hydrochloride.
The incidence of adverse effects of metformin hydrochloride is higher than tolbutamide , common gastrointestinal reactions are anorexia, nausea, vomiting, abdominal pain, diarrhea, occasional metallic taste in the mouth, bad breath, nausea, loss of appetite and diarrhea and other gastrointestinal reactions, sometimes hypoglycemia is visible .
Since the biguanide drugs enhance sugar anaerobic glycolysis, and inhibit glycogen generation, small number of patients may suffer with ketosis or lactic acidosis, which should be particularly vigilant, but metformin effect is weak , adverse reactions are only 1/50 of other biguanides, and it has rapid clearance, there are no accumulation in the liver, it rarely induces lactic acidosis, sometimes there is mild increase in blood lactate. patients with heart, liver, kidney diseases are prone to these adverse reactions, diabetes patients with these types of complications are hanged. It can reduce the absorption of vitamin B12, but it seldom causes anemia. The following cases are contraindications:
1. Pregnant and lactating women, children under 10 years of age, 80 years of age or older.
2. Diabetic ketoacidosis, diabetic hyperglycemic hyperosmolar syndrome, diabetes lactic acidosis.
3. Severe liver and kidney dysfunction, blood urea nitrogen and creatinine higher than normal, hypovolemic shock, heart failure, AMI, in vivo hypoxic condition such as heart failure, pulmonary insufficiency, or any systemic hypoxia circumstances and other serious heart and lung diseases.
4. Severe infection or trauma, major surgery, clinical hypotension , hypoxia and so on.
5. Complications with severe diabetic nephropathy and retinopathy. When there are symptoms,the drug should be immediately discontinued; cimetidine can reduce the renal excretion of metformin hydrochloride, agar types can reduce the absorption of metformin, patients must check liver and kidney function and cardiac ketones regularly.
6. Alcoholics, vitamin B12 and folate deficiency which are not corrected.

9.4 Application

The product belongs to hypoglycemic agents. It can be used in patients with type Ⅱ diabetes to reduce fasting and postprandial hyperglycemia, HbAlc can be decreased by 1% to 2%, hypoglycemic mechanism of this product may be: I increase the sensitivity of peripheral tissues to insulin, increases insulin-mediated glucose utilization . II increase glucose utilization of non-insulin dependent tissues, such as brain, blood cells, kidney medulla, intestine, skin and the like. III inhibit hepatic gluconeogenesis effect, reduce hepatic glucose output. IV inhibit glucose uptake by intestinal cells.
Indications: For mild diabetes.
Metformin hydrochloride is an anti-diabetic agent, reducing blood glucose levels, and improving insulin sensitivity. Its metabolites (including the inhibition of hepatic gluconeogenesis) is activated through LKB1-AMPK (AMP-activated protein kinase) path.
Hypoglycemic agents, it is used for non-insulin-dependent diabetes. Rat oral LD50 of 1000 mg/kg.

View all

9.5 Production method: After the salifying of dimethylamine and the reaction with dicyandiamide , the product is derived.

9.6 Chemical Properties: Crystalline Solid

9.7 Uses: An oral hypoglycemic agent

9.8 Uses: Anti-diabetic and anti-cancer activity

9.9 Definition: ChEBI: A hydrochloride resulting from the reaction of metformin with one molar equivalent of hydrogen chloride.

9.10 Brand name: Fortamet (Andrx); Glucophage (Bristol-Myers Squibb); Glumetza (Depomed); Riomet(Ranbaxy).

9.11 Biological Activity: Antidiabetic agent; lowers plasma glucose levels and improves insulin sensitivity. Inhibits hepatic gluconeogenesis via activation of the LKB1/AMPK pathway. Displays antiproliferative effects in cancer cell lines.

10. Computational chemical data

Molecular Weight: 165.62458g/mol
Molecular Formula: C₄H₁₂ClN₅
Compound Is Canonicalized: True
XLogP3-AA: null
Exact Mass: 165.0781231
Monoisotopic Mass: 165.0781231
Complexity: 132
Rotatable Bond Count: 2
Hydrogen Bond Donor Count: 4
Hydrogen Bond Acceptor Count: 1
Topological Polar Surface Area: 91.5
Heavy Atom Count: 10
Defined Atom Stereocenter Count: 0
Undefined Atom Stereocenter Count: 0
Defined Bond Stereocenter Count: 0
Undefined Bond Stereocenter Count: 0
Isotope Atom Count: 0
Covalently-Bonded Unit Count: 2
CACTVS Substructure Key Fingerprint: AAADccBjgAAEAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAFAAQAAAAAAAAAAQDAANAAAAgAAAAJAAAAAGAAAABAAAIAACAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA==

11. Recommended Suppliers

Global332SuppliersView all >>

Wuhan Xiju Biotechnology Co., Ltd. Diamond member

2YRS

Products:My whatsapp:+86 13043111536 cas no.1451-82-7,79099-07-3,5449-12-7,5337-93-9,49851-31-2,288573-56-8
Tel:86-311-13043111536
Email:Rachel@wh-xiju.com

High Quality Metformin Hydrochloride CAS 1115-70-4 / Metformin HCl

Purity:99%Packing: 200kg/bag FOB
Price: 20 USD/kg
Time: 2023/05/30

Inquire

Hebei Crovell Biotech Co. Ltd Diamond member

3YRS

Products:Cosmetic Raw Materials,solvents,etc.
Tel:86-311-66562153
Email:breeduan@crovellbio.com

Factory Supply Metformin Hydrochloride CAS 1115-70-4

Purity:99%Packing: 200kg/bag FOB
Price: 1 USD/kilogram
Time: 2023/05/30

Inquire

Henan Yuanlong Biotechnology Co.,Ltd. Diamond member

1YR

Products:PMK ethyl glycidate,28578-16-7 ,bmk,5449-12-7,71368-80-4,bromazolam
Tel:0371-60331257-+86
Email:henan2@yuanlongbio.com

Factory Supply Metformin hydrochloride 99% in Stock

Purity:99%Packing: 200kg/bag FOB
Price: 10 USD/kg
Time: 2023/05/30

Inquire

Hebei Bester Biotechnology Co., Ltd. Diamond member

1YR

Products:pmk powder ;pmk oil ;bmk powder ;bmk oil ;Protonitazene hcl ; Bromazolam ; Metonitazene; 2-Bromo-4'-methylpropiophenone ;
Tel:+86-186-33020931
Email:olivia@chbbest.com

China Factory Supply high purity CAS 1115-70-4 Metformin hydrochloride HCI