CH623594A5 - Process for the preparation of 2-[bis(2-chloroethyl)amino]-1-oxa-3-aza-2-phosphacyclohexane 2-oxide with optical activity - Google Patents

Process for the preparation of 2-[bis(2-chloroethyl)amino]-1-oxa-3-aza-2-phosphacyclohexane 2-oxide with optical activity Download PDF

Info

Publication number: CH623594A5
Authority: CH; Switzerland
Prior art keywords: chloroethyl; bis; oxa; aza; amino
Prior art date: 1975-10-06

Application number

CH1266376A

Other languages

German (de)

English (en)

Inventor

Wojciech Jacek Stec

Ryszard Kinas

Krzysztof Pankiewicz

Original Assignee

Polska Akad Nauk Centrum

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1975-10-06

Filing date

1976-10-06

Publication date

1981-06-15

1976-10-06 Application filed by Polska Akad Nauk Centrum filed Critical Polska Akad Nauk Centrum

1981-06-15 Publication of CH623594A5 publication Critical patent/CH623594A5/de

Links

CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 title description 9
238000000034 method Methods 0.000 title description 7
230000003287 optical effect Effects 0.000 title description 4
238000002360 preparation method Methods 0.000 title description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
229960004397 cyclophosphamide Drugs 0.000 description 6
150000001412 amines Chemical class 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
239000000203 mixture Substances 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000007788 liquid Substances 0.000 description 4
238000004949 mass spectrometry Methods 0.000 description 4
239000000047 product Substances 0.000 description 4
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
239000007859 condensation product Substances 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
-1 β-chloroethyl Chemical group 0.000 description 3
RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
150000001793 charged compounds Chemical class 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
239000012043 crude product Substances 0.000 description 2
239000000824 cytostatic agent Substances 0.000 description 2
239000003814 drug Substances 0.000 description 2
239000003480 eluent Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
229910052763 palladium Inorganic materials 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
239000002904 solvent Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
GWISQAMZNKBUCW-JTQLQIEISA-N (2S)-2-[2-(2-chloroethyl)hydrazinyl]-3-phenylpropanoic acid Chemical compound ClCCNN[C@H](C(=O)O)CC1=CC=CC=C1 GWISQAMZNKBUCW-JTQLQIEISA-N 0.000 description 1
CMSMOCZEIVJLDB-AWEZNQCLSA-N (2s)-n,n-bis(2-chloroethyl)-2-oxo-1,3,2$l^{5}-oxazaphosphinan-2-amine Chemical compound ClCCN(CCCl)[P@]1(=O)NCCCO1 CMSMOCZEIVJLDB-AWEZNQCLSA-N 0.000 description 1
238000005160 1H NMR spectroscopy Methods 0.000 description 1
125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
238000004679 31P NMR spectroscopy Methods 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
238000005481 NMR spectroscopy Methods 0.000 description 1
YMMSGNIQKABREQ-UHFFFAOYSA-N O-dichlorophosphorylhydroxylamine Chemical compound NOP(=O)(Cl)Cl YMMSGNIQKABREQ-UHFFFAOYSA-N 0.000 description 1
206010033128 Ovarian cancer Diseases 0.000 description 1
206010061535 Ovarian neoplasm Diseases 0.000 description 1
208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
CFZLNSBZTUMWNS-UHFFFAOYSA-N benzene;chloroform;propan-2-one Chemical compound CC(C)=O.ClC(Cl)Cl.C1=CC=CC=C1 CFZLNSBZTUMWNS-UHFFFAOYSA-N 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
GTVRLHPVICIJFQ-UHFFFAOYSA-N hexane;tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl.CCCCCC GTVRLHPVICIJFQ-UHFFFAOYSA-N 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
238000002955 isolation Methods 0.000 description 1
208000003747 lymphoid leukemia Diseases 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
229940126601 medicinal product Drugs 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
230000002980 postoperative effect Effects 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
- C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
- C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
- C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
- C07F9/65846—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring the phosphorus atom being part of a six-membered ring which may be condensed with another ring system

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Biochemistry (AREA)
General Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CH1266376A 1975-10-06 1976-10-06 Process for the preparation of 2-[bis(2-chloroethyl)amino]-1-oxa-3-aza-2-phosphacyclohexane 2-oxide with optical activity CH623594A5 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
PL18381075A PL100390B1 (pl)	1975-10-06	1975-10-06	Sposob wytwarzania 2-tlenku-2-/bis/2-chloroetylo/-amino/-1-/okso-3-aza-2-fosfacykloheksanu/cyklofosfamidu/o czynnosci optycznej

Publications (1)

Publication Number	Publication Date
CH623594A5 true CH623594A5 (en)	1981-06-15

Family

ID=19973783

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH1266376A CH623594A5 (en)	1975-10-06	1976-10-06	Process for the preparation of 2-[bis(2-chloroethyl)amino]-1-oxa-3-aza-2-phosphacyclohexane 2-oxide with optical activity

Country Status (4)

Country	Link
CH (1)	CH623594A5 (pl)
DE (1)	DE2644905C3 (pl)
GB (1)	GB1553984A (pl)
PL (1)	PL100390B1 (pl)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS54157580A (en) *	1978-05-29	1979-12-12	Otsuka Pharmaceut Co Ltd	Optically active oxazaphosphorine derivative
JPS5826919B2 (ja) *	1978-11-07	1983-06-06	大塚製薬株式会社	シクロ↓−１，３，２↓−オキサアザホスホル誘導体の製造法
DE3132221A1 (de) *	1981-08-14	1983-05-19	Behringwerke Ag, 3550 Marburg	Neue cyclophosphamid-derivate, verfahren zu ihrer herstellung und ihre verwendung
WO1997022614A1 (en) *	1995-12-19	1997-06-26	Darwin Discovery Limited	Ifosfamide, analogues thereof and their preparation

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NL222157A (pl)	1956-12-20

1975
- 1975-10-06 PL PL18381075A patent/PL100390B1/pl unknown
1976
- 1976-10-05 DE DE19762644905 patent/DE2644905C3/de not_active Expired
- 1976-10-06 GB GB4148076A patent/GB1553984A/en not_active Expired
- 1976-10-06 CH CH1266376A patent/CH623594A5/de not_active IP Right Cessation

Also Published As

Publication number	Publication date
GB1553984A (en)	1979-10-17
PL100390B1 (pl)	1978-09-30
DE2644905C3 (de)	1979-11-22
DE2644905A1 (de)	1977-04-14
DE2644905B2 (de)	1979-03-29

Legal Events

Date	Code	Title	Description
1982-06-30	PL	Patent ceased
2024-10-31	PL	Patent ceased

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