Diamino butylic acid

There is, of course, no paucity of examples using heteroatom-based nucleophiles. For example, aziridine-2-/-butyl carboxylate 102 reacts with primary amines to give the dialkylated diamino-propionic acid derivatives 103, which are interesting precursors for the synthesis of cyclosporin analogs. Again, attack occurs overwhelmingly at the B-carbon [95TL4955]. 

The Maruoka group described an efficient enantioselective synthesis of optically active a-methyl serine derivatives by using their structurally simpHfied catalyst (S)-36b under mild phase-transfer conditions [107]. The asymmetric synthesis of a-alkyl cysteines, a-alkyl-a,p-diamino propionic acids, a-alkyl homoserines, and a-alkyl homocysteines was also carried out via the asymmetric phase-transfer catalytic a-alkylation of thiazoline-4-carboxylic acid tert-butyl esters 75, imidazoHne-4-carboxylic acid tert-butyl esters 76, and the six-membered ring substrates 77 and 78 [108]. 

Reaction of 4-chloro-6-fluoropyrido[3,4- pyrimidine 59 with [3-methyl-4-(pyridin-3-yloxy)phenyl]amine 60, followed by coupling the formed amine 61 with (3-azabicyclo[3.1.0]hex-6-yl)carbamic acid fi r7-butyl ester, afforded the substituted derivative 62 <2002EPP1249451>. Compound 59 was also reacted with 3-bromoaniline to give the 4-anilino derivative 63 that upon treatment with either methyl- or dimethylamine gave the corresponding 4,6-diamino derivatives 64 (Scheme 2) <1997W09726259, 1995W09519774>. 

Chloro-l,10-phenanthroline (69) reacts with the sodium salt of tert-butyl cyanoacetate to give the intermediate 105, which with cold hydrochloric acid affords 2-cyanomethyl-1,10-phenanthroline (106).345 2-Chloro-1,10-phenanthroline also participates in the Ullmann reaction to afford 2,2 -bi-(l,10-phenanthroline) (I07).346 5,5 -Bi-(l,10-phenanthroline) was also prepared, but by a different route starting from 8,8 -diamino-6,6 -biquinoline. 

An effective reagent is aqueous hypophosphorus acid, and an example of its use has been described in detail for the synthesis of 3,3 -dimethylbiphenyl from 4,4 -diamino-3,3 -dimethylbiphenyl (o-tolidine).30 As the latter compound is carcinogenic its preparation is ill-advised. More recently the deamination of diazonium salts with t-butyl nitrite in dimethylformamide has been shown to have wide applicability.31 The reaction proceeds smoothly at 65 °C with the evolution of nitrogen gas, the volume of which may be measured and used to monitor the reaction. The mechanism of the reaction is thought to involve the following radical sequence in which the solvent (DMF = solH), is the hydrogen donor. 

More recently Galivan et al. [283] described a synthesis of y-fluoroMTX (VIII.99) involving condensation of di-t-butyl A -[4-(A -methylamino)ben-zoyl]-y-fluoro-L-glutamate with 2,4-diamino-6-bromomethylpteridine, followed by hydrolysis of the ester groups with trifluoroacetic acid. The overall yield was 45 %, and two products with erythro and threo stereochemistry were shown to be present in equal amounts by F-NMR and ion-exchange HPLC. The proton NMR spectrum of the mixture, taken in DjO-DCl solution, showed the /l-CHj protons as a multiplet at b 2.94 and the y-CHF proton as a markedly deshielded multiplet at b 5.42. 

Diamino-t-triazines 172-175 were prepared by condensation of the appropriate nitrile 171 with dicyanodi-amide 169 (Equation 25). 6-(Hydroxymethyl)-2,4-diamino-r-triazine 175 was prepared according to the method of Sims by protection of glycolonitrile as its butyl vinyl ether, subsequent conversion to the corresponding 2,4-diamino-t-triazine, and deprotection with acid <1996JOG6371>. 

Readily available chiral cyclopropenimine (13) catalyses Mannich reactions of A-Boc-aldimines (14) and glycine imines (15), with yields/rZe/ee up to 97/98/95%." The vicinal diamino stereoarray of the products (16) allows access to many useful derivatives, and the t-butyl ester of the product (16, = BuO is amenable to acidic deprotection. In the... 

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