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Chlorambucil

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Chlorambucil

EINECS 206-162-0
CAS No. 305-03-3 Density 1.248 g/cm3
PSA 40.54000 LogP 3.37790
Solubility <0.01 g/100 mL at 22 °C in water Melting Point 65-70 °C
Formula C14H19Cl2NO2 Boiling Point 460.09 °C at 760 mmHg
Molecular Weight 304.216 Flash Point 232.054 °C
Transport Information UN 2811 6.1/PG 3 Appearance beige powder
Safety 53-26-45 Risk Codes 45-25-36/37/38
Molecular Structure Molecular Structure of 305-03-3 (305-03-3) Hazard Symbols ToxicT
Synonyms

Butyricacid, 4-[p-[bis(2-chloroethyl)amino]phenyl]- (8CI);4-[Bis(2-chloroethyl)amino]benzenebutanoic acid;Ambochlorin;Amboclorin;CB 1348;Chloraminophene;Ecloril;Leukeran;Leukeran Tablets;Linfolizin;Linfolysin;Lympholysin;NCI 3088;NSC 3088;g-[p-Di(2-chloroethyl)aminophenyl]butyricacid;Chlorambucil;

Article Data 38

Chlorambucil Synthetic route

2033-24-1

cycl-isopropylidene malonate

500590-36-3

2-(4-(N,N-bis(2-chloroethyl)amino)phenyl)acetaldehyde

305-03-3

chlorambucil

Conditions
ConditionsYield
With formic acid; triethylamine at 50 - 95℃; for 5h; Temperature;76.9%

4-(4-(bis(2-chloroethyl)amino)phenyl)-4-oxobutanoic acid

305-03-3

chlorambucil

Conditions
ConditionsYield
With formic acid; 1,1,1,3',3',3'-hexafluoro-propanol; water at 80℃; for 2h; Sealed tube; chemoselective reaction;54%
79481-83-7

methyl 4-(4-(bis(2-chloroethyl)amino)phenyl)butanoate

305-03-3

chlorambucil

Conditions
ConditionsYield
With hydrogenchloride In water at 60℃; for 1h;53.1%
With hydrogenchloride 1.) 60 deg C, 30 min, 2.) reflux, 10 min; Yield given;
With hydrogenchloride Heating;

4-(4-(bis(2-chloroethyl)amino)phenyl)-N-(quinolin-8-yl)butanamide

305-03-3

chlorambucil

Conditions
ConditionsYield
With water; sodium hydroxide In water for 12h; Reflux;41%
75-21-8

oxirane

20637-09-6

methyl 4-(4-aminophenyl)butanoate

305-03-3

chlorambucil

Conditions
ConditionsYield
With acetic acid Erwaermen des Reaktionsprodukts mit POCl3 in Benzol und Erhitzen des erhaltenen Esters mit konz. wss. HCl;
20637-09-6

methyl 4-(4-aminophenyl)butanoate

305-03-3

chlorambucil

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: acetic acid
2: phosphorus oxychloride / toluene / Heating
3: hydrochloric acid / Heating
View Scheme
Multi-step reaction with 3 steps
1: AcOH / tetrahydrofuran / 48 h / 110 - 120 °C
2: POCl3 / benzene / 1 h / Heating
3: concd. HCl / 1.) 60 deg C, 30 min, 2.) reflux, 10 min
View Scheme
130198-76-4

methyl 3-<4-phenyl>butyrate

305-03-3

chlorambucil

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: phosphorus oxychloride / toluene / Heating
2: hydrochloric acid / Heating
View Scheme
Multi-step reaction with 2 steps
1: POCl3 / benzene / 1 h / Heating
2: concd. HCl / 1.) 60 deg C, 30 min, 2.) reflux, 10 min
View Scheme
20637-02-9

methyl 4-(4-nitrophenyl)butanoate

305-03-3

chlorambucil

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: H2 / Pd/C / ethyl acetate
2: AcOH / tetrahydrofuran / 48 h / 110 - 120 °C
3: POCl3 / benzene / 1 h / Heating
4: concd. HCl / 1.) 60 deg C, 30 min, 2.) reflux, 10 min
View Scheme
901771-68-4

(3β)-3-hydroxyandrost-5-en-17-one 4-{4-[di(2-chloroethyl)amino]phenyl}butyrate

305-03-3

chlorambucil

Conditions
ConditionsYield
With porcine liver esterase; disodium hydrogenphosphate; sodium dihydrogenphosphate; potassium chloride; sodium chloride In ethanol; water at 37℃; for 24h; Enzymatic reaction;
1165715-35-4

(3β)-3-hydroxyandrost-5-en-17-one 4-{4-[di(2-chloroethyl)amino]-3-nitrophenyl}butyrate

305-03-3

chlorambucil

Conditions
ConditionsYield
With porcine liver esterase; disodium hydrogenphosphate; sodium dihydrogenphosphate; potassium chloride; sodium chloride In ethanol; water at 37℃; for 24h; Enzymatic reaction;

Chlorambucil Chemical Properties

Name of Substance: Chlorambucil
CAS Registry Number: 305-03-3
Synonyms: 4-(Bis(2-chloroethyl)amino)benzenebutanoic acid ; 4-(Bis(2-chloroethyl)amino)phenylbutyric acid ; 4-(p-(Bis(2-chloroethyl)amino)phenyl)butyric acid ; 4-14-00-01715 (Beilstein Handbook Reference) ; AI3-26083 ; Ambochlorin ; Amboclorin ; BRN 0999011 ; Benzenebutanoic acid, 4-(bis(2-chloroethyl)amino)- ; Butanoic acid, 4-(bis(2-chloroethyl)amino) benzene ; Butyric acid, 4-(p-(bis(2-chloroethyl)amino)phenyl) ; CB 1348 ; CCRIS 126 ; Cb l348 ; Chloorambucol ; Chlorambucil ; Chlorambucilum ; Chlorambucilum [INN-Latin] ; Chloraminophen ; Chloraminophene ; Chlorbutin ; Chlorbutine ; Chlorbutinum ; Chloroambucil ; Chlorobutin ; Chlorobutine ; Clorambucile ; Clorambucile [DCIT] ; Clorambucilo ; Clorambucilo [INN-Spanish] ; EINECS 206-162-0 ; Ecloril ; Elcoril ; Elcorin ; HSDB 3026 ; Kyselina 4-(N,N-bis-(2-chlorethyl)-p-aminofenyl)maselna ; Kyselina 4-(N,N-bis-(2-chlorethyl)-p-aminofenyl)maselna [Czech] ; Leukeran ; Linfolizin  ; Linfolysin ; Lympholysin ; N,N-Di-2-chloroethyl-gamma-p-aminophenylbutyric acid ; N,N-Di-2-chloroethyl-gamma-para-aminophenyl butyric acid ; NCI-C03485 ; NSC 3088 ; NSC-3088 ; Phenylbuttersaeure-lost ; Phenylbuttersaeure-lost [German] ; Phenylbutyric acid nitrogen mustard ; RCRA waste number U035 ; UNII-18D0SL7309 ; gamma-(p-Bis(2-chloroethyl)aminophenyl)butyric acid ; gamma-(p-Di(2-chloroethyl)aminophenyl)butyric acid ; gamma-(p-bis(2-chloroethyl)aminophenyl)butyricacid ; p-(N,N-Di-2-chlorethylaminophenyl)butyric acid ; p-(N,N-Di-2-chloroethyl)aminophenyl butyric acid ; p-N,N-Di-(beta-chloroethyl)aminophenyl butyric acid ; para-(Di(2-chloroethyl)aminophenyl)butyric acid ; para-N,N-Di(beta-chloroethyl)aminophenyl butyric acid ; Benzenebutanoic acid, 4-(bis(2-chloroethyl)amino)- ; Butyric acid, 4-(p-bis(2-chloroethyl)aminophenyl)- 
IUPAC Name: 4-[4-[bis(2-chloroethyl)amino]phenyl]butanoic acid 
Molecular Weight: 304.21216 [g/mol]
Molecular Formula: C14H19Cl2NO2
XLogP3: 1.7
H-Bond Donor: 1
H-Bond Acceptor: 3
Melting Point: 65-70 °C
Surface Tension: 48.7 dyne/cm
Density: 1.248 g/cm3
Flash Point: 232.1 °C Enthalpy of
Vaporization: 75.94 kJ/mol
Boiling Point: 460.1 °C at 760 mmHg
Vapour Pressure: 2.92E-09 mmHg at 25°C
Following is the molecular structure of Chlorambucil (CAS NO.305-03-3) is:

Chlorambucil Uses

 Chlorambucil (CAS NO.305-03-3) has been mainly used in the treatment of chronic lymphocytic leukemia. It has been used for treating some types of non-Hodgkin lymphoma, Waldenström macroglobulinemia, polycythemia vera, trophoblastic neoplasms, and ovarian carcinoma. Also it has been used as an immunosuppressive drug for various autoimmune and inflammatory conditions, such as nephrotic syndrome. Currenttly ,its use is mainly in chronic lymphocytic leukemia, as it is well tolerated by most patients, though chlorambucil has been largely replaced by fludarabine as first-line treatment in younger patients.

Chlorambucil Toxicity Data With Reference

Organism Test Type Route Reported Dose (Normalized Dose) Effect Source
dog LDLo intravenous 3mg/kg (3mg/kg) GASTROINTESTINAL: OTHER CHANGES

BLOOD: OTHER CHANGES
Cancer Chemotherapy Reports, Part 2. Vol. 2, Pg. 201, 1965.
man TDLo oral 3571ug/kg (3.571mg/kg) BEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLD Journal of Toxicology, Clinical Toxicology. Vol. 20, Pg. 361, 1983.
monkey LDLo intravenous 3mg/kg (3mg/kg) GASTROINTESTINAL: OTHER CHANGES

BLOOD: OTHER CHANGES
Cancer Chemotherapy Reports, Part 2. Vol. 2, Pg. 201, 1965.
mouse LD50 intraperitoneal 20mg/kg (20mg/kg)   British UK Patent Application. Vol. #2028335,
mouse LD50 oral 80mg/kg (80mg/kg)   British UK Patent Application. Vol. #2028335,
mouse LD50 subcutaneous 26mg/kg (26mg/kg)   British UK Patent Application. Vol. #2028335,
rat LD50 intracrebral > 400ug/kg (0.4mg/kg)   Journal of Pharmacy and Pharmacology. Vol. 18, Pg. 760, 1966.
rat LD50 intraperitoneal 14mg/kg (14mg/kg)   Biochemical Pharmacology. Vol. 13, Pg. 969, 1964.
rat LD50 oral 76mg/kg (76mg/kg)   Food and Chemical Toxicology. Vol. 22, Pg. 665, 1984.
rat LDLo subcutaneous 32mg/kg (32mg/kg)   European Journal of Cancer. Vol. 13, Pg. 873, 1977.
women TDLo oral 82600ug/kg (82.6mg/kg) LUNGS, THORAX, OR RESPIRATION: FIBROSIS (INTERSTITIAL)

LUNGS, THORAX, OR RESPIRATION: COUGH

LUNGS, THORAX, OR RESPIRATION: DYSPNEA
Cancer Vol. 41, Pg. 455, 1978.

Chlorambucil Consensus Reports

NTP 10th Report on Carcinogens. IARC Cancer Review: Group 1 IMEMDT    IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man . 7 , 1987,p. 144.(World Health Organization, Internation Agency for Research on Cancer,Lyon, France.: ) (Single copies can be ordered from WHO Publications Centre U.S.A., 49 Sheridan Avenue, Albany, NY 12210) ; Human Inadequate Evidence IMEMDT    IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man . 9 , 1975,p. 125.(World Health Organization, Internation Agency for Research on Cancer,Lyon, France.: ) (Single copies can be ordered from WHO Publications Centre U.S.A., 49 Sheridan Avenue, Albany, NY 12210) ; Human Limited Evidence IMEMDT    IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man . 26 , 1981,p. 115.(World Health Organization, Internation Agency for Research on Cancer,Lyon, France.: ) (Single copies can be ordered from WHO Publications Centre U.S.A., 49 Sheridan Avenue, Albany, NY 12210) ; Animal Limited Evidence IMEMDT    IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man . 26 , 1981,p. 115.(World Health Organization, Internation Agency for Research on Cancer,Lyon, France.: ) (Single copies can be ordered from WHO Publications Centre U.S.A., 49 Sheridan Avenue, Albany, NY 12210) ; Animal Sufficient Evidence IMEMDT    IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man . 9 , 1975,p. 125.(World Health Organization, Internation Agency for Research on Cancer,Lyon, France.: ) (Single copies can be ordered from WHO Publications Centre U.S.A., 49 Sheridan Avenue, Albany, NY 12210) . EPA Genetic Toxicology Program.

Chlorambucil Safety Profile

Safty information about Chlorambucil (CAS NO.305-03-3) is:
Confirmed carcinogen producing leukemia. Experimental carcinogenic and neoplastigenic data. Poison by ingestion, intravenous, intraperitoneal, and subcutaneous routes. Human systemic effects by ingestion: convulsions, cough, dyspnea, and interstitial fibrosis. Human reproductive effects by ingestion and possibly other routes: changes in spermatogenesis, menstrual cycle changes or disorders, and teratogenic effects of the fetal urogenital system. Experimental teratogenic and reproductive effects. Human mutation data reported. An anti-neoplastic agent. When heated to decomposition it emits very toxic fumes of Cl and NOx
Hazard Codes:
ToxicT
Risk Statements:
R45:May cause cancer. 
R25 :Toxic if swallowed. 
R36/37/38:Irritating to eyes, respiratory system and skin.
Safety Statements:
S53:Avoid exposure - obtain special instructions before use. 
S26: In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. 
S45:In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.)
RIDADR: UN 2811 6.1/PG 3
WGK Germany: 3
RTECS: ES7525000
HazardClass: 6.1(b)
PackingGroup: III

Chlorambucil Specification

 Chlorambucil (CAS NO.305-03-3) is a white to pale beige crystalline or granular powder with a slight odor. And it is a chemotherapy drug , also it insoluble in water.It is an alkylating agent.

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