Amino-pyrazoles and -indazoles

The basicity and the protonation site of 3-amino, 4-amino, 5-amino 1-methyl-, and 1-phenyl-pyrazoles has been determined most protonate on the pyrazole Nj ring nitrogen (only 4-amino-pyrazoles protonate on the amino group) 85JHC997,85MRC367,89JCS(P2)1941 . 

Transformation of 5-aminopyrazoles into 5-(pyrrol-l-yl)pyrazoles has been achieved by means of 2,5-dimethoxytetrahydrofuran 94EJM233 which is the first step for the synthesis of pyrazolo-[4.3-/]pyrrolo[l,2-fl]diazepines, a new class of anxiolytics (see Section 3.01.13.2). Pyrazole 5-iminophosphoranes have been used by Wamhoff 94JOC3985 as starting materials for the synthesis of zwitterionic heteropolycyclic pyrazoles. 

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This reactivity of A-unsubstituted amino-pyrazoles and -indazoles which can be regarded as 1,3-diamino derivatives has been used to build a great variety of fused six-membered heterocycles such as the 1,2,4-triazine derivatives (540) and (541), the 1,3,5-triazine derivatives (542) and (543), and benzothiadiazines (544). 

Amination at an azole ring nitrogen is known for Af-unsubstituted azoles. Thus 4,5-diphenyl-1,2,3-triazole with hydroxylamine-O-sulfonic acid gives approximately equal amounts of the 1- (104) and 2-amino derivatives (105) (74AHC(16)33). Pyrazole affords (106) and indazole gives comparable amounts of the 1- and 2-amino derivatives. 

Ethyl (2E)-3-(dimethylamino)-2-(5-ethoxy-l-phenyl-lH-pyrazol-3-yl) propenoate (36) was prepared in two steps from ethyl (5-oxo-l-phenyl-4,5-dihydro-lH-pyrazol-3-yl)acetate (12) by treatment with ethyl bromide in ethanol under reflux to give ethyl (5-ethoxy-l-phenyl-lH-phenyl-3-yl) acetate (35), followed by treatment with DMFDM A in toluene under reflux. Compound 36 reacted with anilines, methyl glycinate hydrochloride, 3-amino-lf-f-indazole and 3-amino-5-methylisoxazol in ethanol in the... 

Amino-l-methylindazolium salt reacts with acetylacetone differently in comparison with TV-aminobenzimidazolium salts [Eq. (91)] (76CPB2 267). This is explained partly by the decreased CH-acidity of the pyrazole ring and partly because the product of the primary cyclization (376) is not stabilized by ring opening, but is aromatized by the oxidant to pyraz-olo[l,5-/)]indazole (377). 

The log P of 3-hydroxy-4-amino-5-trifluoromethylpyrazole has been determined <89JMC2il6>. The log P values of l-(l-adamantyl)pyrazole, 3.05 ( ), l-(l-adamantyl)indazole, 4.33 (59), and 2-(l-adamantyl)indazole, 3.68 (60) were determined by HPLC. From these values, the n value of the... 

Nitrogen Systems.—A review on the synthesis of pyrrolo[l,2-a]indoles (754) and related systems has appeared. Treatment of azobenzene (755) with 2,6-dimethylphenyl isocyanide (756) in the presence of dicobalt octacarbonyl yields a mixture of the imino-indazoline (757) and the indazolo-indazole (758)." Heating 5-amino-l-o-chlorophenyl-pyrazoles (759 R = CN or C02Et) in DMF in the presence of copper oxide yields the pyrazolo-benzimidazoles (760)." ... 

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