Cyclophosphamide

Base Information

• Chemical Name: Cyclophosphamide
• CAS No.: 50-18-0
• Deprecated CAS: 60007-95-6,75526-90-8
• Molecular Formula: C7H15Cl2N2O2P
• Molecular Weight: 261.088
• Hs Code.: 2924299090
• European Community (EC) Number: 200-015-4
• ICSC Number: 0689
• NSC Number: 756711,273034,273033,26271
• UN Number: 2811,3464
• UNII: 6UXW23996M
• DSSTox Substance ID: DTXSID5020364
• Nikkaji Number: J441.625B,J3.385.421H,J2.793F,J3.202F
• Wikipedia: Cyclophosphamide
• Wikidata: Q408524
• NCI Thesaurus Code: C61694
• RXCUI: 1545988
• Metabolomics Workbench ID: 42870
• ChEMBL ID: CHEMBL88
• Mol file: 50-18-0.mol

Synonyms:(+,-)-2-(bis(2-Chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-Oxide Monohydrate;B 518;B-518;B518;Cyclophosphamide;Cyclophosphamide Anhydrous;Cyclophosphamide Monohydrate;Cyclophosphamide, (R)-Isomer;Cyclophosphamide, (S)-Isomer;Cyclophosphane;Cytophosphan;Cytophosphane;Cytoxan;Endoxan;Neosar;NSC 26271;NSC-26271;NSC26271;Procytox;Sendoxan

Chemical Property of Cyclophosphamide

Chemical Property:

• Appearance/Colour: white crystalline powder
• Vapor Pressure: 0.000115mmHg at 25°C
• Melting Point: 41-45 °C
• Boiling Point: 336.1 °C at 760 mmHg
• PKA: 2.84±0.20(Predicted)
• Flash Point: 157.1 °C
• PSA: 51.38000
• Density: 1.33 g/cm³
• LogP: 2.21280
• Storage Temp.: Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
• Solubility.: ≥11.85 mg/mL in H2O with gentle warming and ultrasonic; ≥13.05 mg/mL in DMSO; ≥50.8 mg/mL in EtOH
• Water Solubility.: Soluble. 1-5 g/100 mL at 23 ºC
• XLogP3: 0.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 5
• Exact Mass: 260.0248201
• Heavy Atom Count: 14
• Complexity: 212
• Transport DOT Label: Poison

Purity/Quality:

99% ^*data from raw suppliers

Cyclophosphamide ≥99%(HPLC) ^*data from reagent suppliers

Safty Information:

• Safety Statements: 22-24/25

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Chemical Classes: Other Classes -> Other Organic Compounds
• Drug Classes: Antineoplastic Agents, Alkylating Agents
• Canonical SMILES: C1CNP(=O)(OC1)N(CCCl)CCCl
• Recent ClinicalTrials: Fludarabine and Rituximab With or Without Lenalidomide or Cyclophosphamide in Treating Patients With Symptomatic Chronic Lymphocytic Leukemia
• Recent EU Clinical Trials: Phase 2b Single Arm Study of Maveropepimut-S and Low-Dose Cyclophosphamide in Subjects with Platinum-Resistant, Epithelial Ovarian
• Recent NIPH Clinical Trials: A Phase 3 Trial of Neoadjuvant T-DXd Monotherapy or T-DXd followed by THP Compared to ddAC-THP in Participants with High-risk HER2-positive Early-stage Breast Cancer (DESTINY-Breast11)
• Inhalation Risk: A harmful concentration of airborne particles can be reached quickly when dispersed, especially if powdered.
• Effects of Short Term Exposure: The substance may cause effects on the blood, bladder, central nervous system and heart.
• Effects of Long Term Exposure: The substance may have effects on the blood, bladder, lungs and bone marrow. This may result in leucopenia, cystitis and pulmonary fibrosis. This substance is carcinogenic to humans. May cause heritable genetic damage to human germ cells. Causes serious reproductive toxicity in humans.
• Uses: Cyclophosphamide USP is used to treat acute and chronic lymphocytic leukemia; lung cancer; rhabdomyosarcoma; neuroblastoma; ovarian and mammary carcinoma; multiple myeloma; lymphosarcoma; Burkitt’s lymphoma; Hodgkin’s disease; retinoblastoma; mycosis fungoides An anti-proliferative agent that regulates Bax and Bcl-2 expression.
• Indications: Cyclophosphamide (Cytoxan) is the most versatile and useful of the nitrogen mustards. Preclinical testing showed it to have a favorable therapeutic index and to possess the broadest spectrum of antitumor activity of all alkylating agents. As with the other nitrogen mustards, cyclophosphamide administration results in the formation of cross-links within DNA due to a reaction of the two chloroethyl moieties of cyclophosphamide with adjacent nucleotide bases. Cyclophosphamide must be activated metabolically by microsomal enzymes of the cytochrome P450 system before ionization of the chloride atoms and formation of the cyclic ethylenimmonium ion can occur. The metabolites phosphoramide mustard and acrolein are thought to be the ultimate active cytotoxic moiety derived from cyclophosphamide.
• Therapeutic Function: Antineoplastic
• Clinical Use: Cyclophosphamide is a component of CMF (cyclophosphamide, methotrexate, 5-fluorouracil) and other drug combinations used in the treatment of breast cancer. Cyclophosphamide in combination may produce complete remissions in some patients with ovarian cancer and oat cell (small cell) lung cancer. Other tumors in which beneficial results have been reported include non–oat cell lung cancers, various sarcomas, neuroblastoma, and carcinomas of the testes, cervix, and bladder. Cyclophosphamide also can be employed as an alternative to azathioprine in suppressing immunological rejection of transplant organs.
• Drug interactions: Potentially hazardous interactions with other drugs Antipsychotics: avoid with clozapine, increased risk of agranulocytosis. Cytotoxics: increased toxicity with high-dose cyclophosphamide and pentostatin - avoid.

Technology Process of Cyclophosphamide

There total 9 articles about Cyclophosphamide which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 92.3%

1,2-dichloro-ethane (107-06-2,52399-93-6) + 2-chloro-2-oxo-1,3,2λ5-oxazaphosphinane (5638-58-4) → cyclophosphamide (50-18-0)

Guidance literature:

With ammonia; at 120 ℃; for 2h; under 3040.2 Torr; Molecular sieve;

Reference yield: 77.6%

bis-(2-chloroethyl)amine hydrochloride (821-48-7) + propan-1-ol-3-amine (156-87-6) → cyclophosphamide (50-18-0)

Guidance literature:

bis-(2-chloroethyl)amine hydrochloride; With 4-methyl-morpholine; trichlorophosphate; In neat (no solvent); at 4 - 20 ℃; for 5h; Green chemistry;

propan-1-ol-3-amine; In neat (no solvent); at 4 - 20 ℃; for 18h; Reagent/catalyst; Green chemistry;

Reference yield: 22.0%

3-(benzyloxy)cyclophosphamide (78336-01-3) → cyclophosphamide (50-18-0) + 3-hydroxycyclophosphamide (78336-02-4)

Guidance literature:

With hydrogen; palladium on activated charcoal; In ethyl acetate; for 72h; under 2068.6 - 2327.2 Torr; Yield given; Ambient temperature;

DOI:10.1021/jm00144a007

upstream raw materials:

N,N-di(2-chloroethyl)amidophosphoric acid dichloride

propan-1-ol-3-amine

3-(benzyloxy)cyclophosphamide

(2-Oxo-2λ⁵-[1,3,2]oxazaphosphinan-2-yl)-bis-(2-trimethylsilanyloxy-ethyl)-amine

Downstream raw materials:

Phosphoric acid mono-{3-[2-(2-chloro-ethylamino)-ethylamino]-propyl} ester

4-hydroxycyclophosphamide

4-hydroperoxycyclophosphamide

ethanol

Refernces

• 1、 -. "Synthetic method for cyclophosphoramide". Paragraph 0026; 0029; 0030; 0033-0037. . Retrieved 2019/04/11.
• 2、 -. "Solvent-Free Process for the Preparation of Cyclophosphamide". Paragraph 0039; 0040; 0041; 0042. . Retrieved 2014/03/25.