3-Ethyl-2-methyl-5-(morpholin-4-ylmethyl)-1,5,6,7-tetrahydroindol-4-one Property

Melting point:

180-181°

Boiling point:

462.9±45.0 °C(Predicted)

Density 

1.140±0.06 g/cm3(Predicted)

solubility 

H₂O: 19 mg/mL

form 

solid

pka

pKa 6.9(H2O,t =25,I=0.2) (Uncertain)

color 

off-white

CAS DataBase Reference

7416-34-4(CAS DataBase Reference)

NIST Chemistry Reference

Indol-4(5h)-one, 3-ethyl-6,7-dihydro-2-methyl-5-(morpholinomethyl)-(7416-34-4)

Safety

Hazard Codes 

Xn

Risk Statements 

22

RIDADR 

UN 2811 6.1/PG 3

WGK Germany 

3

RTECS 

NM3325000

Hazardous Substances Data

7416-34-4(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P270Do not eat, drink or smoke when using this product.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P330Rinse mouth.

P501Dispose of contents/container to..…

3-Ethyl-2-methyl-5-(morpholin-4-ylmethyl)-1,5,6,7-tetrahydroindol-4-one Chemical Properties,Usage,Production

Originator

Moban,Endo,US,1974

Uses

Molindone is a more active antipsychotic than chloropromzine. Its sedative effect is less expressed. Side effects are also expressed less than with powerful neuroleptics. It facilitates the reduction of spontaneous movements and aggressiveness, and is used for treatment of psychotic disturbances, particularly in cases of chronic and severe schizophrenia.

Uses

Antipsychotic.

Definition

ChEBI: Molindone is a member of indoles.

Manufacturing Process

Diethyl ketone may be reacted with methyl nitrite and that product in turn reacted with cyclohexan-1,3-dione to give 3-ethyl-4,5,6,7-tetrahydro-2- methyl-4-oxoindole.
3-ethyl-4,5,6,7-tetrahydro-2-methyl-4-oxoindole 14.1 g (0.08 mol), 14.8 g morpholine hydrochloride (0.12 mol), and 3.6 g paraformaldehyde (0.12 mol) were refluxed in 200 ml ethanol for 40 hours. The solution was evaporated to dryness in vacuo on a steam bath and the residue digested with a mixture of 150 ml water and 10 ml 2N HCl. An insoluble residue of unreacted starting material was filtered off. To the acid solution, ammonia water was added dropwise with stirring and the amine crystallized out. It was purified by dissolving in 1N HCl and addition of ammonia, then by 2 crystallizations from benzene followed by 2 crystallizations from isopropanol, to yield 3-ethyl- 4,5,6,7-tetrahydro-2-methyl-4-oxoindole, melting point 180°C to 181°C.

brand name

Moban (Endo).

Therapeutic Function

Antipsychotic

Side effects

Molindone hydrochloride, a tetrahydro-indolone derivative, is a neuroleptic agent that is structurally unrelated to any of the other marketed neuroleptics. Molindone is less potent than haloperidol at blocking D2 receptors; however, it nonetheless can produce extrapyramidal side effects.

Synthesis

Molindone, 3-ethyl-6,7-dihydro-2-methyl-5-(morpholinomethyl)indol-4(5H)- one (6.4.3), is synthesized by the nitrozation of diethylketone using nitric acid or methylnitrite into nitrozodiethylketone (6.4.1). Reduction of this product with zinc in acetic acid into 2-aminodiethylketone in the presence of cyclohexandion-1,3 gives 3-ethyl-2-methyl- 4,5,6,7-tetrahydroindol-4-one (6.4.2). Aminomethylation of this product using morpholine and formaldehyde gives molindone (6.4.3) [51¨C52].

Metabolism

Metabolism studies in humans show molindone to be rapidly absorbed and metabolized when given orally. There are 36 recognized metabolites, with less than 2 to 3% unmetabolized molindone being excreted in urine and feces. Clinical studies show that the antipsychotic effects of molindone last more than 24 hours, suggesting that one or more metabolites may contribute to its activity in vivo (62).