- Substituted 2-methylene-1,3-oxazolidines, -1,3-thiazolidines, -1,3-benzothiazines, -1,3-oxazines, and substituted imidazopyrimidinediones from Cl(CH2)nNCO and Cl(CH2)nNCS and active methylene compounds
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The reaction of ω-chloroalkyl isocyanates Cl(CH2) nNCO (n = 2 (2), 3 (4)) and isothiocyanate Cl(CH2) 2-NCS (3) with active methylene compounds CH2YY′ 1 in the presence of Et3N or Na give 2-YY′-methylene-1,3- oxazolidines, (E,Z)-1,3-thiazolidines, and 1,3-oxazines from 2, 3, and 4, respectively. 2-(Chloromethyl)-phenyl isocyanate 8 gives with 1 the corresponding benzo-oxazines. Ethyl 2-isothiocyanatobenzoate 10 gives the corresponding benzothiazolinone, whereas the analogous isocyanate 12 gives noncyclic enols. Ethoxycarbonyl isothiocyanate 14 gives an open-chain thioenol or an enol-thioamide. The cyanoamides CH2(CN)CONHR, R = H, Me, CHPh2, give with Et3N and 2 the bicyclic imidazopyrimidinediones 16, derived from two molecules of 2, but with their preformed Na salt they give the 1,3-oxazolidines. Reaction of cyanoacetamide with 3 in the presence of Na gave a tricyclic triaza(thia)indacene, derived from two molecules of 3. A reaction mechanism involving an initial attack of the anion 1- on the N=C=X (X = O, S) moiety gives an anion 18, which cyclizes intramolecularly and after tautomerization gives the mono-ring heterocycle. With the cyanoamides, the N- site of the ambident ion 18 attacks another molecule of 2 giving the anion 20, which by intramolecular attack on the CN, followed by expulsion of the Cl- gives the bicyclic 16 after tautomerization.
- Basheer, Ahmad,Rappoport, Zvi
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Read Online
- Method for preparing high-purity carmustine
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The invention provides a method for preparing high-purity carmustine. Specifically, the preparation method comprises a step of recrystallizing a crude carmustine product with an organic solvent, wherein the organic solvent is a mixed solvent of an alcohol solvent and water, and the alcohol solvent is preferably at least one selected from the group consisting of methanol, ethanol and isopropanol. The method can be used for preparing high-purity carmustine.
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Paragraph 0062-0063; 0065
(2020/04/17)
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- SAFE AND EFFICIENT PROCESS FOR THE PREPARATION OF CARMUSTINE
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Carmustine may be safely and efficiently produced by reacting 2-chloroethylamine hydrochloride and 1,1′-carbonyldiimidazole to afford 1,3-bis(2-chloroethyl)-1-urea, followed by nitrosation to give the final product.
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Paragraph 0092-0097
(2017/09/25)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF 1,3-BIS(2-CHLOROETHYL)-1-NITROSOUREA
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The present invention relates to an improved process for the preparation of 1,3-bis(2-chloroethyl)-1 -nitrosourea compound of formual-1 which is represented by the following structural formula:
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Page/Page column 9; 10
(2017/09/27)
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- PROCESS FOR PREPARATION OF CARMUSTINE
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The present invention relates to an improved process for preparation of carmustine (I). The present invention also relates to preparation of 1,3-bis(2-chloroethyl)urea (II) an intermediate used in preparation of carmustine.
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Page/Page column 8
(2017/11/10)
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- Degradation and disposal of some antineoplastic drugs
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Bulk quantities and pharmaceutical preparations of the antineoplastic drugs carmustine (BCNU), lomustine (CCNU), chlorozotocin, N-[2-chloroethyl]-N'-[2,6-dioxo-3-piperidinyl]-N-nitrosourea (PCNU), methyl CCNU, mechlorethamine, melphalan, chlorambucil, cyclophosphamide, ifosfamide, uracil mustard, and spiromustine may be degraded using nickel-aluminium alloy in KOH solution. The drugs are completely destroyed and only nonmutagenic reaction mixtures are produced. destruction of cyclophosphamide in tablets requires refluxing in HCl before the nickel-aluminium alloy reduction. Streptozotocin, chlorambucil, and mechlorethamine may be degraded using an excess of saturated bicarbonate solution. The nitrosourea drugs BCNU, CCNU, chlorozotocin, PCNU, methyl CCNU, and streptozotocin were also degraded using hydrogen bromide in glacial acetic acid. The drugs were completely destroyed but some of the reaction mixtures were mutagenic and the products were found to be, in some instances, the corresponding mutagenic, denitrosated compounds.
- Lunn,Sansone,Andrews,Hellwig
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p. 652 - 659
(2007/10/02)
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- Convenient Methods for Syntheses of Active Carbamates, Ureas and Nitrosoureas Using N,N'-disuccinimido Carbonate (DSC)
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The reaction of DSC and amino compounds afforded the corresponding carbamates which were able to be converted into ureas and nitrosoureas.
- Takeda, Kazuyoshi,Akagi, Yoshie,Saiki, Atsuko,Tsukahara, Toshiko,Ogura, Haruo
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p. 4569 - 4572
(2007/10/02)
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