54400-62-3 Usage
Originator
Butamisole
hydrochloride,American
Cyanamid (AHP)
Manufacturing Process
To a stirred solution of 110.0 g (0.62 mole) of 3'-acetylacetanilide in 2400 ml
of chloroform is added dropwise a solution of 33.0 ml (102.9 g; 0.644 mole) of bromine in 240 ml of chloroform. The solution is stirred 1 h and the
resultant precipitate is then filtered, washed with ether and dried. The solid is
stirred in a large volume of water to give an oily precipitate which crystallizes
on further stirring. The solid is filtered, washed with water and then 2-
propanol, dried to give 148.34 g of the 3'-bromacetylacetanilide, melting point
108.5-110°C (recrystallized from 2-propanol).
A solution of 5.12 g (0.020 mole) of 3'-bromoacetylacetanilide in 70 ml of
acetone is added to a stirred solution of 2.04 g (0.020 mole) of 2-amino-2-
thiazoline in 30 ml of acetone. The mixture is stirred 1.5 h and the precipitate
then filtered, washed with acetone and dried to give 6.00 g of 3'-[(2-imino-3-
thiazolidinyl)acetyl]acetaniIide hydrobromide, meltng point 275-277°C
(recrystallization from water).
To a stirred slurry of 63.47 g (0.177 mole) of 3'-[(2-imino-3-thiazolidinyl)
acetyl]acetanilide hydrobromide in 1 L of 95% ethanol, maintained at 5°C, is
added 5.70 g (0.15 mole) of sodium borohyride. After stirring 40 min an
additional 4.10 g of sodium borohydride is added and the mixture is acidified
with hydrochloric acid and evaporated under reduced pressure. The residue is
partitioned between chloroform and dilute aqueous ammonium hydroxide. Two
further chloroform extracts are combined with the original, washed with brine,
dried (sodium sulfate) and evaporated to give an oil. Treatment with acetone
gives 6.77 g (48%) of 3'-[l-hydroxy-2-(2-imino-3-
thiazolidinyl)ethyl]acetanilide hydrochloride as white crystalline, melting point
235-237°C.
Addition of 5.00 g (0.0158 mole) of 3'-[1-hydroxy-2-(2-imino-3-
thiazolidinyl)ethyl]acetanilide hydrochloride to 15 ml of concentrated sulfuric
icid is carried out in small increments over 0.5 h. The orange solution is
stirred an additional 1 h, poured onto ice and made basic with concentrated
ammonium hydroxide. The aqueous base is extracted twice with chloroform
and the combined organic layers washed with water, brine, dried (sodium
sulfate) and evaporated at reduced pressure to give 3.32 g (80% crude yield)
of the 3'-(2,3,5,6-tetrahydroimidazo[2,1-b]thiazol-6-yl)acetanilide, melting
point 164-166°C (recrystallization from 2-propanol).
A solution of 1.00 g (0.0038 mole) of 3'-(2,3,5,6-tetrahydroimidazo[2,1-
b]thiazol-6-yl)acetanilide in 17 ml of 6 N hydrochloric acid is heated at reflux
for 2.5 h and then allowed to stand overnight at room temperature. The
solution is concentrated at reduced pressure, made basic with concentrated
aqueous sodium hydroxide while cooling and then extracted with 3 portions of
chloroform. The combined organic layers are washed with brine, dried (sodium
sulfate) and evaporated to give 0.84 g of an oil, i.e., 6-(m-aminophenyl)-
2,3,5,6-tetrahydroimidazo[2,1-b]thiazole free base. The oil is dissolved in hot
methanol and strongly acidified with hydrogen chloride in 2-propanol.
Evaporation of the solution give the 6-(m-aminophenyl)-2,3,5,6-
tetrahydroimidazo[2,1-b]thiazole dihydrochloride, melting point 198-201°C
(crystallization from 2-propanol).
2.2 g (0.010 mole) of 6-(m-aminophenyl)-2,3,5,6-tetrahydroimidazo[2,1-
b]thiazole dihydrochloride is disolved in a mixture of 15 ml methanol and 15
ml water and the pH is adjusted to about 6 with an aqueous hydrochloric acid
solution. This solution is then added to 3.2 g (0.020 mole) of isobutyric
anhydride. The mixture is allowed to stand at room temperature for 12 h. The reaction mixture is then added to a mixture of 100 ml methylene chloride and
50 ml water and then made basic (pH 10) with an aqueous sodium hydroxide.
The methylene chloride layer is removed and the water layer is washed twice
with 75 ml of fresh methylene chloride. The methylene chloride extract are
then combined, dried over magnesium sulfate, and the methylene chloride
evaporated leaving a tacky solid. The free base of the product is recrystallized
from a chloroformethyl ether mixture. The yield of the 3'-(2,3,5,6-
tetrahydroimidazo[2,1-b]thiazol-6-yl)isobutyranilide is 1.6 g (55%).
Check Digit Verification of cas no
The CAS Registry Mumber 54400-62-3 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,4,4,0 and 0 respectively; the second part has 2 digits, 6 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 54400-62:
(7*5)+(6*4)+(5*4)+(4*0)+(3*0)+(2*6)+(1*2)=93
93 % 10 = 3
So 54400-62-3 is a valid CAS Registry Number.
