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Risperidal

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Name

Risperidal

EINECS 600-733-1
CAS No. 106266-06-2 Density 1.383 g/cm3
PSA 64.16000 LogP 3.52830
Solubility 44.74mg/L(25 oC) Melting Point 170 °C
Formula C23H27FN4O2 Boiling Point 572.4 °C at 760 mmHg
Molecular Weight 410.491 Flash Point 300 °C
Transport Information UN 3249 Appearance crystalline solid
Safety 28-36-45 Risk Codes 25
Molecular Structure Molecular Structure of 106266-06-2 (Risperidone) Hazard Symbols ToxicT
Synonyms

Risperdal (TN);Risperidone;3-(2-(4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperidino)ethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido(1,2-a)pyrimidin-4-one;Apexidone;BRN 4891881;HSDB 7580;Psychodal;R 64 766;Risperdal Consta;Risperidona;Rispolept;

Article Data 18

Risperidal Synthetic route

132961-05-8

C23H28F2N4O2

106266-06-2

Risperidone

Conditions
ConditionsYield
With borax; sodium hydroxide In ethanol at 70℃; for 0.5h;94.9%
With borax; potassium hydroxide In ethanol at 40 - 70℃; for 0.5h;83.9%
With potassium hydroxide In ethanol; water at 80℃; for 1 - 5h; Product distribution / selectivity;

3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride

84163-13-3

6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride

106266-06-2

Risperidone

Conditions
ConditionsYield
With sodium carbonate In methanol at 73 - 75℃; for 4 - 4.5h; Product distribution / selectivity;93.6%
With sodium carbonate In water at 25 - 55℃; for 9h; Product distribution / selectivity;
With sodium carbonate In water; acetonitrile at 25 - 75℃; for 8h; Product distribution / selectivity;
63234-80-0

3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one

84163-13-3

6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride

106266-06-2

Risperidone

Conditions
ConditionsYield
With sodium carbonate In water at 110 - 120℃; for 0.666667h; Product distribution / selectivity;93.2%
With sodium carbonate; potassium iodide In N,N-dimethyl-formamide at 80℃; for 10h; Temperature;76.9%
63234-80-0

3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one

84163-77-9

6-fluoro-3-(4-piperidinyl)benzo[d]isoxazole

106266-06-2

Risperidone

Conditions
ConditionsYield
With sodium carbonate In methanol at 73 - 75℃; for 4 - 4.5h; Product distribution / selectivity;92.8%
With N-ethyl-N,N-diisopropylamine In methanol at 45 - 50℃; for 70 - 100h; Product distribution / selectivity;77.8%
With sodium carbonate In water at 85 - 90℃; for 4h;73%
With potassium iodide; sodium carbonate In water; isopropyl alcohol
885706-66-1

3-(2-iodoethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one

84163-13-3

6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole hydrochloride

106266-06-2

Risperidone

Conditions
ConditionsYield
With potassium carbonate In acetone for 6h; Heating / reflux;87.4%

3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride

135634-18-3

(2,4-difluorophenyl)-piperidin-4-yl-methanone oxime hydrochloride

106266-06-2

Risperidone

Conditions
ConditionsYield
With sodium carbonate; potassium iodide In acetonitrile for 32h; Heating / reflux;81%
With potassium carbonate; potassium iodide In acetonitrile for 30h; Heating / reflux;79%
With potassium carbonate; potassium iodide In DMF (N,N-dimethyl-formamide) at 95 - 100℃; for 18h;77%
With potassium carbonate; potassium iodide In 4-methyl-2-pentanone at 100 - 105℃; for 30h;73%
599173-41-8

3-{2-[4-(6-fluorobenzo[d]isoxazol-3-yl)-piperidin-1-yl]-vinyl}-2-methyl-6,7,8,9-tetrahydro-pyrido[1,2-a]pyrimidin-4-one

106266-06-2

Risperidone

Conditions
ConditionsYield
With sodium cyanoborohydride; acetic acid In ethanol at 20℃; for 2.5h;70.9%
63234-80-0

3-(2-chloroethyl)-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one

2,4-difluorophenyl-(4-piperidinyl)methanone oxime hydrochloride

106266-06-2

Risperidone

Conditions
ConditionsYield
With potassium hydroxide In water at 120 - 130℃; for 1.5h;40%

3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride

84163-46-2

(2,4-difluorophenyl)(4-piperidinyl)methanone oxime

106266-06-2

Risperidone

Conditions
ConditionsYield
Stage #1: 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride; 2,4-difluorophenyl-4-piperidinylmethanone oxime With sodium carbonate; potassium iodide In isopropyl alcohol at 20 - 82℃; for 4.16667h; Heating / reflux;
Stage #2: With potassium hydroxide In water; isopropyl alcohol at 30 - 40℃; for 6h;
99.4 %Chromat.
Stage #1: 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride; 2,4-difluorophenyl-4-piperidinylmethanone oxime With sodium carbonate; potassium iodide In isopropyl alcohol at 20 - 82℃; for 5.16667h; Heating / reflux;
Stage #2: With piperidine In isopropyl alcohol at 20 - 30℃; for 12h;
Stage #1: 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride; 2,4-difluorophenyl-4-piperidinylmethanone oxime With sodium carbonate; potassium iodide In isopropyl alcohol at 20 - 82℃; for 5.16667h; Heating / reflux;
Stage #2: With sodium hydroxide In water; isopropyl alcohol at 25 - 30℃; for 12h;
Stage #1: 3-(2-chloroethyl)-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one monohydrochloride; 2,4-difluorophenyl-4-piperidinylmethanone oxime With sodium hydroxide; potassium iodide In isopropyl alcohol at 20 - 82℃; for 5.16667h; Heating / reflux;
Stage #2: With sodium hydroxide In water; isopropyl alcohol at 23 - 30℃; for 12h;
158697-66-6

C23H28F2N4O2

106266-06-2

Risperidone

Conditions
ConditionsYield
In acetonitrile

Risperidal History

The drug of Risperidone was developed by Janssen-Cilag and first released in 1994. In 1993, Risperidone was approved by the United States Food and Drug Administration (FDA) for the treatment of schizophrenia. On August 22, 2007, risperidone was approved as the only drug agent available for treatment of schizophrenia in youth ages 13–17; it was also approved for treatment of bipolar disorder in youth and children ages 10–17 at the same day, joining lithium.

Risperidal Specification

The CAS registry number of Risperidone is 106266-06-2. In addition, the molecular formula is C23H27FN4O2. The IUPAC name is 3-[2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl]-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one. What's more, it contains the functional groups of benzisoxazole and piperidine as part of its molecular structure. And it is associated with significant weight gain and metabolic problems, as well as tardive dyskinesia and neuroleptic malignant syndrome. 

Physical properties about  Risperidone are:
 (1)ACD/LogP: 2.68; (2)ACD/LogD (pH 5.5): 0.179; (3)ACD/LogD (pH 7.4): 1.886; (4)ACD/BCF (pH 5.5): 1; (5)ACD/BCF (pH 7.4): 10.314; (6)ACD/KOC (pH 5.5): 2.159; (7)ACD/KOC (pH 7.4): 110.125; (8)#H bond acceptors: 6; (9)#Freely Rotating Bonds: 4; (10)Polar Surface Area: 61.94 Å2; (11)Index of Refraction: 1.677; (12)Molar Refractivity: 111.747 cm3; (13)Molar Volume: 296.84 cm3; (14)Polarizability: 44.3 ×10-24cm3; (15)Surface Tension: 51.106 dyne/cm; (16)Density: 1.383 g/cm3; (17)Flash Point: 299.966 °C; (18)Enthalpy of Vaporization: 85.804 kJ/mol; (19)Boiling Point: 572.382 °C at 760 mmHg.

Preparation of Risperidone:
 The preparation can start from the acylation of 4-formyl chloride-1-acetylpiperidine with benzoisooxazole in the presence of catalyst aluminium trichloride. Through deacetylation by hydrochloric acid and cyclization reaction you can get a benzoisooxazole derivative. Then the benzoisooxazole derivative can react with 3-chloroethyl-2-methyl-4H-pyrido[1,2-α ]pyrimidine-4-one hydrochloride to give the desired product in the presence of sodium carbonate, potassium iodide and dimethylcarboxamide. The reaction temperature should be controlled at 85-90 °C with heating. And the yield is about 46%.

Uses of Risperidone:
 It is used to treat schizophrenia (including adolescent schizophrenia), schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism. In addition, it was reported to successfully treat the symptoms of phencyclidine (PCP) psychosis due to acute intoxication and chronic use.

When you are using  Risperidone, please be cautious about it as the following:
This chemical is toxic if swallowed. hen you are using it, wear suitable protective clothing. If contact it with skin, wash it immediately with plenty of ... (to be specified by the manufacturer). Moreover, in case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.).

You can still convert the following datas into molecular structure:
(1)SMILES: Cc1c(c(=O)n2c(n1)CCCC2)CCN3CCC(CC3)c4c5ccc(cc5on4)F
(2)InChI: InChI=1/C23H27FN4O2/c1-15-18(23(29)28-10-3-2-4-21(28)25-15)9-13-27-11-7-16(8-12-27)22-19-6-5-17(24)14-20(19)30-26-22/h5-6,14,16H,2-4,7-13H2,1H3
(3)InChIKey: RAPZEAPATHNIPO-UHFFFAOYAV

The toxicity data of Risperidone is as follows:

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
child TDLo oral 268ug/kg (0.268mg/kg) SENSE ORGANS AND SPECIAL SENSES: OTHER: EYE

BEHAVIORAL: TREMOR

BEHAVIORAL: CHANGES IN MOTOR ACTIVITY (SPECIFIC ASSAY)
Annals of Pharmacotherpy. Vol. 30, Pg. 360, 1996.
dog LD50 intravenous 14100ug/kg (14.1mg/kg)   Journal of Pharmacology and Experimental Therapeutics. Vol. 244, Pg. 685, 1988.
dog LD50 oral 18300ug/kg (18.3mg/kg) BEHAVIORAL: MUSCLE WEAKNESS

LUNGS, THORAX, OR RESPIRATION: RESPIRATORY STIMULATION

GASTROINTESTINAL: "HYPERMOTILITY, DIARRHEA"
Kiso to Rinsho. Clinical Report. Vol. 27, Pg. 2991, 1993.
man TDLo oral 114ug/kg/2D-I (0.114mg/kg) BEHAVIORAL: WAKEFULNESS

BEHAVIORAL: EUPHORIA

BEHAVIORAL: EXCITEMENT
American Journal of Psychiatry. Vol. 153, Pg. 1234, 1996.
man TDLo oral 429ug/kg (0.429mg/kg) SENSE ORGANS AND SPECIAL SENSES: MIOSIS (PUPILLARY CONSTRICTION): EYE

CARDIAC: PULSE RATE INCREASE WITHOUT FALL IN BP

CARDIAC: EKG CHANGES NOT DIAGNOSTIC OF ABOVE
American Journal of Emergency Medicine. Vol. 16, Pg. 498, 1998.
man TDLo oral 429ug/kg/15D- (0.429mg/kg) BRAIN AND COVERINGS: CHANGES IN SURFACE EEG

BEHAVIORAL: ALTERATION OF OPERANT CONDITIONING

BEHAVIORAL: ANOREXIA (HUMAN
Journal of Clinical Psychiatry. Vol. 58, Pg. 323, 1997.
man TDLo oral 3428ug/kg (3.428mg/kg) BEHAVIORAL: "HALLUCINATIONS, DISTORTED PERCEPTIONS"

CARDIAC: EKG CHANGES NOT DIAGNOSTIC OF ABOVE
Annals of Emergency Medicine. Vol. 22, Pg. 1908, 1993.
man TDLo oral 3857ug/kg (3.857mg/kg) BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD

CARDIAC: EKG CHANGES NOT DIAGNOSTIC OF ABOVE

CARDIAC: PULSE RATE
Journal of Toxicology, Clinical Toxicology. Vol. 37, Pg. 893, 1999.
mouse LD50 intravenous 26900ug/kg (26.9mg/kg)   Journal of Pharmacology and Experimental Therapeutics. Vol. 244, Pg. 685, 1988.
mouse LD50 oral 63100ug/kg (63.1mg/kg)   Journal of Pharmacology and Experimental Therapeutics. Vol. 244, Pg. 685, 1988.
rat LD50 intravenous 34300ug/kg (34.3mg/kg) BEHAVIORAL: TREMOR

BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD
Kiso to Rinsho. Clinical Report. Vol. 27, Pg. 2991, 1993.
rat LD50 oral 56600ug/kg (56.6mg/kg)   Journal of Pharmacology and Experimental Therapeutics. Vol. 244, Pg. 685, 1988.
rat LD50 subcutaneous 98mg/kg (98mg/kg) SENSE ORGANS AND SPECIAL SENSES: PTOSIS: EYE

LUNGS, THORAX, OR RESPIRATION: DYSPNEA

BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)
Kiso to Rinsho. Clinical Report. Vol. 27, Pg. 2991, 1993.
women TDLo oral 400ug/kg (0.4mg/kg) BEHAVIORAL: MUSCLE CONTRACTION OR SPASTICITY)

CARDIAC: PULSE RATE INCREASE WITHOUT FALL IN BP
American Journal of Emergency Medicine. Vol. 16, Pg. 498, 1998.
women TDLo oral 880ug/kg (0.88mg/kg) BEHAVIORAL: SOMNOLENCE (GENERAL DEPRESSED ACTIVITY)

CARDIAC: ARRHYTHMIAS (INCLUDING CHANGES IN CONDUCTION)
American Journal of Emergency Medicine. Vol. 16, Pg. 498, 1998.
women TDLo oral 1840ug/kg (1.84mg/kg) BEHAVIORAL: "HALLUCINATIONS, DISTORTED PERCEPTIONS"

BEHAVIORAL: HEADACHE

VASCULAR: BP LOWERING NOT CHARACTERIZED IN AUTONOMIC SECTION
Journal of Clinical Psychiatry. Vol. 56, Pg. 514, 1995.
women TDLo oral 2mg/kg (2mg/kg) CARDIAC: ARRHYTHMIAS (INCLUDING CHANGES IN CONDUCTION)

CARDIAC: PULSE RATE INCREASE WITHOUT FALL IN BP

VASCULAR: BP ELEVATION NOT CHARACTERIZED IN AUTONOMIC SECTION
Journal of Clinical Pyschopharmacology. Vol. 17, Pg. 325, 1997.
women TDLo oral 2200ug/kg (2.2mg/kg) CARDIAC: ARRHYTHMIAS (INCLUDING CHANGES IN CONDUCTION)

VASCULAR: BP ELEVATION NOT CHARACTERIZED IN AUTONOMIC SECTION
Therapie. Vol. 52, Pg. 155, 1997.
women TDLo oral 648mg/kg/77W- (648mg/kg) BEHAVIORAL: CHANGES IN MOTOR ACTIVITY (SPECIFIC ASSAY)

BEHAVIORAL: ATAXIA

BEHAVIORAL: MUSCLE CONTRACTION OR SPASTICITY)
Journal of Clinical Psychiatry. Vol. 59, Pg. 478, 1998.

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