Purification, general procedures amines

N -Ethyl-jK-toluidine has been obtained by passing m-toluidine and ethyl alcohol over a catalyst at high temperatures,1 and by the use of ethyl />-toluenesulfonate 2 as an alkylating agent. The present method of purification is a modification of a general procedure for secondary amines developed by Diepolder.3... 

General Procedure for Preparation of Triazones 5a-f. 264 mg (3 mmol) /V,/V-di-metliylurea, 1 g paraformaldehyde, 3 mmol primary amine 4a-f and 2 g montmorillonite K-10 were irradiated by microwave in a Teflon vessel. The reaction mixture was filtered and washed with water. The organic phase was separated and dried with Na2S04 and concentrated by vacuum distillation. Purification of the... 

Ethynyl-2-(ethynylphenyl)-4-nitroaniIine. See the general procedure for the deprotection of trimethylsilyl-protected alkynes. 74 (0.10 g, 0.27 mmol) was deprotected to the terminal alkyne and the free amine using the procedure described above using K2CO3 (0.19 g, 1.35 mmol), MeOH (15 mL), and CH2CI2 (15 mL). The reaction mixture was allowed to stir at room temperature for 2 h. The resultant mixture was subjected to an aqueous workup as described above. Due to the instability of conjugated terminal alkynes, the material was immediately used in the next step without additional purification or identification. 

General procedure for insertion reaction of isocyanates into 2,6-dia-zasemibullvaiene 6-la. 2,6-Diazasemibullvalene 6-la (0.5 mmol, 136 mg) in 2 mL of toluene was treated with isocyanate (1.0 mmol), and the reaction mixture was stirred at 100 °C for 8 h. After the removal of solvent in vacuum, purification by column chromatography (silica gel, petroleum ether/diethyl ether/triethyl-amine = 100 5 1) gave 6-8a, 6-8b, or 6-8c as pure products. 

The three-step procedure described here illustrates a convenient, general route to di-tert-alkylamines. Extensive purification or isolation of intermediates is not required. The reactions are easily monitored. Only in the final step is the exclusion of air and moisture necessary. It should be noted that tert-butyl-tert-octylamine is considerably more hindered than 2,2,6,6-tetramethylpiperidine. tert-Butyl-tert-octylamine is inert to methyl iodide, while 2,2,6,6-tetramethylpiperidine gives a white precipitate of the pentamethylammonium iodide within minutes upon treatment with methyl iodide at room temperature. The extreme hindrance of this amine has been exploited in the selective deprotonation of carbon adds and in other reactions.10... 

Unsym. subst. melamines can be prepared from cyanuric chloride by successive reaction with 3 different amines. The procedure is quite general. The intermediate monoamino derivatives are not isolated. The diamino derivatives, however, are insoluble in the reaction medium. They are isolated and, without purification, treated with the third amine in a different solvent system.— E 1 mole of di-n-propylamine followed by 1 mole of aq. NaOH added below 5° to a slurry of cyanuric chloride in water-acetone, stirred 1 hr. at 0°, then 1 mole of di-n-butylamine added followed by 1 mole of aq. NaOH without cooling, and kept 5-6 hrs. at 45-50 crude 2-di-n-propylamino-4-di-n-butyl-amino-6-chloro-s-triazine (Y ca. 100%) mixed with n-butanol, heated, 1 mole of dihexylamine added at 55-60° and 1 mole of aq. NaOH at 90-95° at such a rate that the mixture remains just alkaline to phenolphthalein, heating continued 3-4 hrs. at 90-95° -> N2-di-n-propyl-N -di-n-butyl-N -dihexylmelamine (Y 99%). F. e. s. J. R. Campbell and R. E. Hatton, J. Org. Chem. 26, 2786 (1961) 2-chloro-4,6-diamino-s-triazines s. N. N. Mel nikov et al., Khim. Prom. 1961, 703 C. A. 58, 526b. 

The synthesis of ABT-839 H2S04 was completed in eight chemical operations (10 steps total) in an overall yield of 43%. This synthesis was used to produce 4 kg of ABT-839 free amine and 2 kg of ABT-839 H2S04. The general approach was to utilize disconnections similar to those used in the original synthesis with an emphasis on streamlined work-up procedures and a single purification prior to final isolation. The steps for appending the two sidechains to... 

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