1 -ethyl-2-morpholino

C) Preparation of Doxapram Hydrochloride [3,3-Diphenyl-1-Ethyl-4-(2-Morpholino-Ethylj-2-Pyrrolidinone Hydrochloride Monohydrate] A solution of 25 grams (0.076 mol) of 4-(2-chloroethyl)-3,3-diphenyl-1-ethyl-2-pyrrolidinone and 13.3 grams (0.153 mol) of morpholine in 500 ml of absolute ethanol was heated at 95°-120°C for 21 hours in a closed system and concentrated in vacuo. The residue was dissolved in 3(X) ml of two normal hydrochloric acid and extracted with 150 ml of ethyl acetate. A solid crystallized (13 g) during the extraction and was removed by filtration. MP 217°-219°C. The acid extracts were made basic with sodium hydroxide and extracted with ether, and the ether solution was concentrated in vacuo and the residue was suspended in six normal hydrochloric acid. Additional crystalline product formed and was recrystallized from two normal hydrochloric acid. Yield, 10 grams MP 217°-219°C. Total yield, 23 grams (70%). 

The synthesis of this ring system was achieved by the reaction of the ketene aminal 79 with 3-morpholino-l-ethyl-l,2,4-triazinium tetrafluoro-borate 78 to give 80 (89IZV494). Cyclization of 78 with the bifunctional nucleophile 81 gave the pyrrolo[3,2-e][l,2,4]triazinones 82 (88TL1431). This reaction represents the first example of orthocyclization onto the 1,2,4-triazine ring by the addition of dienophiles at C-5,6 (Scheme 20). 

Ethyl 3-chloro-2-quinoxalinecarboxylate gave ethyl 3-p-fluorobenzylamino-2-quinoxalinecarboxylate (109) [H2NCH2C6H4F-P (1 equiv), EtOH, reflux, 13 h 73% analogs likewise]or ethyl 3-morpholino-2-quinoxalinecarboxylate (110) [0[CH2CH2)NH (1 equiv), MeOH, reflux, 2h 34%]. ... 

Ethyl 3-morpholino-2-quinoxalinecarboxylate (78, R = OEt) gave 3-morpho-lino-2-quinoxalinecarbohydrazide (78, R = NHNH2) (H2NNH2 H2O, MeOH, reflux, 8 h 73%). ... 

Ethyl-l-methyl-2(17T)-quinoxalinone 4-oxide Ethyl 3-morpholino-2-quinoxalinecarboxylate Ethyl 6-nitro-2-quinoxalinecarboxylate... 

Ethyl 4-ethyl-3-oxo-3,4-dihydro-2-quinoxalinecarboxylate Ethyl 7-fluoro-3-methyl-6-morpholino-2-quinoxalinecarboxylate Ethyl 7-fluoro-3-methyl-6-morpholino-2-quinoxalinecarboxylate 1,4-dioxide Ethyl 3-formyl-2-quinoxalinecarboxylate... 

Methyl-l//-pyrimido[l,2-rz]quinolin-l-one was obtained by heating isopropylidene 2-[l-(2-quinolylamino)ethy-lidene]malonate in EtOH at 20 °C <2000CCL283>. FVT of ethyl 3-morpholino- and 3-(Ar-methyl-Ar-phenylamino)-... 

GTP was employed for the synthesis of block copolymers with the first block PDMAEMA and the second PDEAEMA, poly[2-(diisopropylamino)e-thyl methacrylate], PDIPAEMA or poly[2-(N-morpholino)ethyl methacrylate], PM EM A (Scheme 33) [87]. The reactions took place under an inert atmosphere in THF at room temperature with l-methoxy-l-trimethylsiloxy-2-methyl-1-propane, MTS, as the initiator and tetra-n-butyl ammonium bibenzoate, TBABB, as the catalyst. Little or no homopolymer contamination was evidenced by SEC analysis. Copolymers in high yields with controlled molecular weights and narrow molecular weight distributions were obtained in all cases. The micellar properties of these materials were studied in aqueous solutions. 

In the course of studies on the synthesis of [l,2,4]triazolo[3,4-A][l,2,4,5]tetrazines, Kotschy et al. investigated the alkylation of the morpholino derivative 13 of this ring system <2000ARK259>. It has been found that ethylation carried out with triethyloxonium tetrafluoroborate took place exclusively on the five-membered ring and yielded a mixture of 1-ethyl 14 and 2-ethyl 15 quaternary salts. 

Fig. 10.1 Structures ofthe fluorescent whitening agents included in this study. Full names DAS 1,4,4 -bis[4-anilino-6-morpholino-1,3,5-triazin-2-yl)-amino]stilbene-2,2 -disulphonate DSBP, 4,4 -bis(2-sulfostyryl)biphenyl BLS, 4,4 -bis(4-chloro-3-sulfostyryl)biphenyl. Internal standard 4,4 -bis-5-ethyl-3-sulfobenzofur-2-yl)biphenyl.

The cyclocondenzation of benzamidine and morpholino- or piperidino-methylenemalonates in boiling ethanol for 2 hr yielded ethyl 2-phenylpyri-midine-5-carboxylate (1330) (64JMC68). 

A benzotriazole-assisted synthesis of ethyl 5-aminoimidazo[2,l-h]thia-zole-6-carboxylate 65 has been developed (96TL1787). Traces of compound 63 were isolated from 2-aminothiazole 23 using benzotriazole and freshly distilled ethyl glyoxylate in benzene, whereas by application of a-benzotria-zolyl-a-morpholino acetate with methyl iodide in THF, 63 was isolated in 40% yield. Subsequent treatment of 63 with potassium cyanide in ethanol at rt involves substitution of the benzotriazole moiety. Intramolecular cycli-zation of 64 yields 65, albeit in 10% yield. a-Ketoester 66 is also obtained (Scheme 3). 

We have recently evaluated the ATRP of a wide range of hydrophilic monomers such as 2-sulfatoethyl methacrylate (SEM), sodium 4-vinylbenzoate (NaVBA), sodium methacrylate (NaMAA), 2-(dimethylamino)ethyl methacrylate (DMA), 2-(iV-morpholino)ethyl methacrylate (MEMA), 2-(diethylamino)ethyl methacrylate (DEA), oligo(ethylene glycol) methacrylate (OEGMA), 2-hydroxyethyl methacrylate (HEMA), glycerol monomethacrylate (GMA), 2-methacryl-oyloxyethyl phosphorylcholine (MPC), and a carboxybetaine-based methacrylate [CBMA]. Their chemical structures and literature references (which contain appropriate experimental details) are summarised in Table 1. 

Transformation of both the ester and nitrile derivatives 726 or 727 into pyrano[2,3-t7 pyridazines 728 or 729, respectively, by treatment with dilute HCl at room temperature involved nucleophilic displacement of the morpholine group by the hydroxyl group with an acidic hydrolysis followed by intramolecular iminolactonization and then hydrolysis of the formed imino group to a carbonyl group. Compounds 726 and 727 were prepared by Vilsmeier-Haack formylation of 2-methyl-5-morpholino-3(2/7)-pyridazinone 724 followed by condensation of the resulting product 725 with either ethyl a-cyanoacetate or malononitrile in EtOH (Scheme 34) <1994H(37)171>. 

Z)-l -Nitro-l-alkene werden in Diethylether an En-amine addiert3- u. Die Additionsreak-tion verlauft weitgehend diastereo- und enantioselektiv. Durch saure Hydrolyse kann das Amin nach der Addition abgespaltcn werden und man erhalt ein Keton. So reagiert 2-Morpholino-3,4-dihydro-naphthalin mit (Z)-2-Nitro-l-phenyl-ethen zu l-(2-Nitro-l-phe-nyl-ethyl) -2-oxo-tetralin. 

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