121514-27-0 Usage
Originator
U 68553B ,Upjohn Company
Manufacturing Process
The solid 5-methoxy-2,2-dicarboxy-2,3-dihydro-1H-phenalene, was
decarboxylated (one carboxyl group removed) by heating in an oil bath at
190°-210°C for 50 min. The resulting liquid was cooled, and the solid was
ground to a fine powder to obtain 37.1 g (98% yield) of the subtitled 2-
carboxyl-5-methoxy-2,3-dihydro-1H-phenalene, melting point 194°-196°C.
A mixture of the 5-methoxy-2,3-dihydro-1H-phenalen-2-yl-carboxylic acid,
(37.1 g; 0.153 mole), 42.1 g (0.153 mole) of diphenyl phosphoryl azide, 17.0
g (0.168 mole) of triethylamine and 1950 ml of dry tert-butyl alcohol was
refluxed for 21 h. The initially formed solution became a suspension. The
solvent was evaporated in vacuo and the residue was taken up in a
chloroform/water mixture. The resulting suspension was filtered. The filtrate
was separated, the aqueous phase was extracted with chloroform, and the
combined organic liquid phases was washed with 5% w/v sodium hydroxide
aqueous solution (3x100 ml), with water and with saturated sodium chloride
salt solution and then dried over magnesium sulfate and evaporated.The
resulting residual yellow solid, 35.9 g, was extracted with boiling
SKELLYSOLVE B brand of hexanes (5x200 ml), the resulting solution was
concentrated to about 300 ml, clarified with diethyl ether and allowed to
crystallize at 0°C to obtain 28.6 g of the 5-methoxy-2-(tertbutoxycarbonylamino)-
2,3-dihydro-1H-phenalene, melting point 113°-115°C.
Trifluoroacetic acid, 85 ml, was added to 30.5 g (0.0958 mole) of the 5-
methoxy-2-(tert-butoxycarbonylamino)-2,3-dihydro-1H-phenalene. The
resulting solution was stirred for 20 min. Ice was then added, and the
resulting mixture was made pH basic with 20% w/w sodium hydroxide in
water solution and stirred for 1 h at room temperature. The mixture was
extracted well with chloroform, the chloroform extract was separated and
washed with water, with saturated sodium chloride solution; dried with
magnesium sulfate, and evaporated to give 18.8 g (92% yield) of the 2-
amino-5-methoxy-2,3-dihydro-1H-phenalene as a brown oil.
This 2-amino-5-methoxy-2,3-dihydro-1H-phenalene was converted to its
hydrochloride salt in methanol with 1.5 N hydrogen chloride in diethyl ether
solution to give 18.11 g of the 2-amino-5-methoxy-2,3-dihydro-1H-phenalene
hydrochloride as colorless needle crystals, melting point 252°C (dec.).
A mixture of 2-amino-5-methoxy-2,3-dihydro-1H-phenalene, 2.6 g (0.0122
mole), released from its hydrochloride, 6.46 g (0.0525 mole) of n-propylbromide, 7.25 g (0.0525 mole) of potassium carbonate and 50 ml of
acetonitrile was refluxed for 20 h. Another 3.3 g of n-propyl bromide, 3.6 g of
potassium carbonate and 25 ml of acetonitrile were added to the reaction
mixture. The mixture was refluxed for 26 h. GC analysis of a sample of the
reaction mixture indicated complete reaction. The mixture was evaporated,
and the residue was taken up in a diethyl ether/water mixture. The organic
liquid layer was washed with saturated sodium chloride (salt) solution and
dried with magnesium sulfate, and evaporated. The residue was dissolved in
petroleum ether (boiling point 30°-60°C), and filtered from some insoluble
brown material, and the filtrate was evaporated to leave the 2-(di-npropylamino)-
5-methoxy-2,3-dihydro-1H-phenalene.
The 2-(di-n-propylamino)-5-methoxy-2,3-dihydro-1H-phenalene was dissolved
in diethyl ether, treated with ethereal hydrogen chloride which resulted in the
formation of the crude gummy solid hydrogen chloride salt. 2.67 g (66%
yield) of the 2-(di-n-propylamino)-5-methoxy-2,3-dihydro-1H-phenalene
hydrochloride, melting point 196°-197°C (crystallized from a methanol/diethyl
ether).
A mixture of 2-(di-n-propylamino)-5-methoxy-2,3-dihydro-1H-phenalene,
(1.65 g; 5.55 mmol), released from the hydrochloride salt, and 20 ml of 48%
aqueous hydrogen bromide solution was heated for 15 min in an oil bath at
125°-130°C. The reaction mixture was evaporated, the residue was dissolved
in a minimum amount of methanol, diethyl ether was added until the mixture
became cloudy, and the mixture was filtered through a filter aid (CELITE) to
remove some oily impurity. The filtrate was diluted with diethyl ether and
seeded. There was obtained 1.28 g (63% yield) of the 2-(di-n-propylamino)-
2,3-dihydro-lH-phenalen-5-ol hydrobromide, melting point 233°-234°C (dec.).
Therapeutic Function
Antipsychotic, Dopamine agonist
Check Digit Verification of cas no
The CAS Registry Mumber 121514-27-0 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,1,5,1 and 4 respectively; the second part has 2 digits, 2 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 121514-27:
(8*1)+(7*2)+(6*1)+(5*5)+(4*1)+(3*4)+(2*2)+(1*7)=80
80 % 10 = 0
So 121514-27-0 is a valid CAS Registry Number.
InChI:InChI=1/C19H25NO.BrH/c1-3-8-20(9-4-2)17-10-14-6-5-7-15-12-18(21)13-16(11-17)19(14)15;/h5-7,12-13,17,21H,3-4,8-11H2,1-2H3;1H
121514-27-0Relevant articles and documents
SYNTHESIS OF 2,3-DIHYDRO-1H-PHENALENE DERIVATIVE BY THE INTRAMOLECULAR DIELS-ALDER REACTION OF BENZYNE WITH FURAN
Darlington, W. H.,Szmuszkovicz, J.
, p. 1883 - 1886 (1988)
2,3-Dihydro-1H-phenalene derivative 1 was synthesized by the intramolecular Diels-Alder reaction (21->22). 2,5-Dimethylpyrrole was used as a protecting group for the primary amine.