Alternate AMT from Gramine Procedure

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Indole derivatives.  XLIV.  Synthesis of indopan [3-(2-aminopropyl) indole] from indole.    
Bulatova, N. N.; Suvorov, N. N.  
Khim.-Farm. Zh.  (1968),  2(2),  27-9.   
Journal  written in Russian.   
CAN 69:77044    AN 1968:477044  

Abstract
Na (0.42 g.) dissolved in 15 ml. abs. EtOH, 95 ml. abs. iso-PrOH, 4.1 g. EtNO2, and 2.9 g. 3-dimethylaminomethylindole added dropwise with intensive stirring, after 20 min. 4.2 g. Me2SO4 in 30 ml. iso-PrOH added, the mixt. stirred at room temp. 1-2 hrs., treated with 300-500 ml. water, extd. with ether, and the product chromatographed and sepd. with 5:1 Et2O-petroleum ether gave 91% 3-(2-nitropropyl)indole (I), b1 174-6°.  a-Methyltryptamine (II), m. 96-8°, was synthesized in 67.2% yield by hydrogenation of I in EtOH in the presence of Raney Ni at 60° at a starting pressure of 50 atm., filtration after 2-4 hrs. and evapn. in vacuo; II hydrochloride (indopan) m. 214-15°; II adipate m. 223-4° (EtOH); II picrate, red, m. 218-19°.
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Indole derivatives.  XLVIII.  Synthesis and pharmacological properties of N-L-a'-glutamyl-a-ethyltryptamine.
Bulatova, N. N.; Trubitsyna, T. K.; Suvorov, N. N.; Mashkovskii, M. D.   
Khim.-Farm. Zh.  (1968),  2(11),  6-9. 
CODEN: KHFZAN  Journal  written in Russian.   
CAN 70:58253    AN 1969:58253

Abstract
PrNO2 (16.8 g.) and gramine (10.2 g.) were added to a soln. of NaOEt (1.46 g. Na and 30 ml. abs. EtOH) and poured into 310 ml. iso-PrOH.  After 25 min. 14.6 g. Me2SO4 in 90 ml. iso-PrOH was added at (less than)35° yielding (overnight) 91% 3-(2-nitrobutyl)-indole (I), m. 90-2°.  Hydrogenation of I in the presence of Raney Ni in EtOH at 60° beginning at 50 atm. 3-4 hrs. yielded 9.5 g. a-ethyltryptamine (II), m. 104-5° (aq. MeOH).  I hydrochloride, adipate, and picrate had m.ps. 218-19°, 212-13° (EtOH), and 202°, resp.  Carbobenzoxy-L-glutamic acid g-benzyl ester (III) prepd. by the method of Hanby et al. (1950) was dissolved in 80 ml. dry tetrahydrofuran (THF), 5.6 ml. Et3N was added at -8 to -10°, followed by 5.6 ml. iso-BuO2CCl and finally 6.58 g. II in 150 ml. THF.  Stirring followed by workup yielded (73%) carbobenzoxy-L-a'-glutamyl-a-ethyltryptamine g-benzyl ester (IV), m. 155-7° (C6H6-C6H12 mixt.).  IV was hydrogenated in an autoclave in 300 ml. MeOH over 1 g. 10% Pd/C at 50° beginning at 40 atm. 4-5 hrs., yielding 5.2 g. N-L-a'-glutamyl-a-ethyl-tryptamine (V), m. 175-6°.  V stimulated the central nervous system of mice, as measured by antagonism to reserpine, but was less active and less toxic than its methyl analog (LD50 for V oral in mice =460 mg./kg. for individual and 145 mg./kg. for grouped mice, and 202.5 and 52.5 mg./kg., resp., with the methyl analog).
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Indole derivatives. X. 5-Acetyl-a-methyltryptamine.
Terzyan, A. G.; Tatevosyan, G. T.
Khim. Nauki  (1962),  15(6),  563-6. 
Journal  written in Russian.   
CAN 59:35470    AN 1963:435470   

Abstract
5-Acetyl-a-methyltryptamine (I) was prepd. for study of its biol. properties.  Prepn. of 2,3-dioxo-6-methylpiperidine 3-p-acetylphenylhydrazone (II): 0.1 mole 6-methyl-3-carbethoxy-2-piperidone and 6 g. KOH in 250 ml. H2O kept overnight at room temp. filtered, the soln. cooled to -5° and 500 ml. cold soln. of p-acetylphenyldiazonium chloride (prepd. from 13.5 g. p-aminoacetophenone, 7.6 g. NaNO3, and 28 ml. concd. HCl) added portionwise, pH adjusted to 4.5 by addn. of 40 ml. AcONa soln., the whole stirred 4 hrs., kept overnight, the orange ppt. filtered off, washed with H2O, dried, and triturated with Et2O, then with 50% EtOH to yield 75.2% II, light-yellow after boiling with C, m. 225-6° (EtOH).  Synthesis of 3-oxo-5-methyl-10-acetyl-3,4,5,6-tetrahydro-b-carboline (III): 0.05 mole II and 60 ml. 85% HCO2H refluxed 5 hrs., cooled, filtered off, washed with H2O, and airdried gave 85.1% III, m. 345-6° (EtOH) (decompn.).  III (0.035 mole), 36 g. KOH, and 550 ml. 60% EtOH was boiled 15 hrs., 200 ml. H2O added, EtOH removed, the residue filtered, the filtrate acidified with AcOH to pH 6, the ppt. filtered off, washed with H2O, and air dried to give 98.2% colorless 5-acetyl-a-methyltryptamine-2-carboxylic acid (IV), m. 329-30° (H2O) (decompn.).  IV (0.025 mole) in 170 ml. 25% HCl and 50 ml. AcOH refluxed 36-40 hrs., filtered, the filtrate basified with NaOH, I filtered off, washed with H2O, dried over KOH, extd. with Et2O several times, and most of Et2O evapd. gave 54% I, m. 146-8°, hydrochloride m. 234-5° (Et2O), picrate m. 150°. Cf. CA 59, 2753e. 
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