Title of Invention

A ONE STEP PROCESS FOR PREPARING DIMETHYLAMINOSULFONATES OF ALKANE DIOLS

Abstract A one step process for preparing a compound of formula I comprising treating the alkane diols of formula II with methylaminosulfonyl chloride containing methylaminosulfonate group at a temperature range of-10 to 30°c in the presence of a base selected from triethylamine, potassium carbonate and sodium hydride in a suitable solvent.
Full Text This invention relates to a one step process for preparing
dimethylaminosulfonates of alkane diols of formula I.
An object of this invention is to propose a process for pre-
paration of novel group of compounds of formula I having an anti
cancerous property.
A further object Of this invention is to (propose a process
for preparing dimethylaminosulfonates of alkane diols with
a good yield.
Further objects and advantages of this invention will be more
apparent from the ensuing description.
At the outset of the description which follows, it is to be
understood that the' ensuing description only illustrates a
particular form of this invention. However, such a particular
form is only an exemplary embodiment, and without intending
to imply any limitation on the scope of this invention is
to be understood as an exemplary embodiment and teaching of
the invention and not intended to be taken restrictively.
According to this invention there is provided a one step process
of preparing a compound of formula I comprising treating the
alkane diols of formula II with methylamincsulfonyl chloride
containing methylaminosulfonate group at a temperature range
of -10 to 30°C in the presence of a base selected from triethyl-
amine, potassium carbonate and sodium hydride in a solvent.
It has been found that the compounds of the general formula
I, can be prepared in moderate to good yields by treating
the respective alkane diols of the general formula II with
methylaminosulfonyl chloride (MeNHSO2 Cl) containing the methylamino-
sulfonate (CH3NHSO2-) group which is transferred in the presence
of a suitable base to furnish the desired compound of the
general formula I.

The bases such as triethylamine, potassium carbonate and sodium
hydride have been used to complete the reaction by k the removal
of hydrogen chloride formed during the reaction.
The reaction can be carried out in suitable solvents (other
than hydroxylic solvents like water, methanol etc) as anhydrous
ethyl acetate and tetrahydrofuran which dissolves both the
alkane diols as well as the reagent. However, when sodium
hydride is used as the base, tetrahydrofuran is the solvent
of choice instead of ethyl acetate as the latter reacts with
this base.
By following the above synthetic process, six new., compounds
(n= 3-8) have been obtained. Out of them, five compounds are
solids (n= 4-8) while one compound is a liquid.
Examles : Preparation of 1,4-Butanodiol dimethylaminosulfonate
Method A: (Triethylamine used as the base)
To a solution of freshly distilled triethylamine (4.2 ml, 30
mmolar parts by weight) and anhydrous ethyl acetate (20 ml
by volume) at 0-5°C was added freshly distilled 1,4-butanediol
(0.9 gm, 10 mmolar parts by weight). The mixture is stirred
at 0-5 C for 15 min to get a clear solution. To this solution
was added dropwise under protection from atmospheric moisture
over a period of ½ an hour, a solution of methylaminosulfonyl
chloride (3.12 g, 24 mmolar parts by weight) in anhydrous ethyl
acetate (6 ml by volume). Immediate precipitation of the white
hydrochloride salt took place. After stirring at 0-5 for 4
hrs, the reaction mixture was warmed to 70-75 C and stirred
at this temperature for 2 hrs and next kept in the freeze overnight
Next day it was filtered under suction to remove the precipitated
hydrochloride salt which was washed with ethyl acetate (5ml
x 2). The filtrate was taken in a seperating funnel and washed
with brine once (5, ml). The solvent was dried over anhydrous
sodium sulphate and distilled off under reduced pressure in
a rota-vac to furnish a viscous oil (2.5gm). The crude product
was kept at 0°C overnight when it became a low melting solid.
The crude reaction product was next passed through a column
of silica gel (50 gm by weight) packed in pet. ether (60-80 C),
and eluted with solvents with increasing polarity. The desired
product was obtained by elution with chloroform-methanol mixture
(95:5 v/v) to furnish a white solid (1.3 gm). This was crystal-
lised from pet. ether (40-60°C)- chloroform mixture to furnish
the pure compound (1.1 gm, effective yield 40.0%); m.pt.55-
56ºC Vmax(KBr) 3314, 2970, 1426, 1349, 1173, 1072, 1032, 879,
827, 724 cm-1; 1H PMR(CDC13) d 1-77-2.0 (4H,m, CH2), 2.83 (6H,
d, J = 7.0 Hz, NCH3), 4.10-4.33 (4H,m,OCH2), 4.67-5.03 (2H,m,NH).
Method B: (Potassium carbonate used as the base)
To a stirred solution of freshly distilled 1 ,4-butanediol (0.9
gm, 10 mmolar parts by weight) in anhydrous ethyl acetate (20
ml by volume) at 0-5 C was added anhydrous powdered potassium
carbonate (2.07 gm, 30 mmolar parts by weight). The mixture
was stirred for 15 mins. To this mixture was added dropwise
over a period of ½ hr, a solution of methylaminosulfonyl chloride
(3.12 gm, 24 mmolar parts by weight) in anhydrous ethyl acetate
(6 ml by volume). After stirring for 4 hrs at 0-5 C, the reaction
mixture was warmed to 70-75 C and maintained at this temp.
for 2 hrs and next kept in the freeze overnight. It was next
worked up in the same manner as that of Method A. Final yield
after crystallisation was 1.2 gm (43.5%).
Method C: (Sodium hydride used as the base)
To an oily suspension of sodium hydride (1.25 gm, 55-57% base
content) was added freshly distilled anhydrous tetrahydrofuran
(8 ml in volume) to remove the adhering oil. Tetrahydrofuran
was removed as far as possible by careful decantation from
the reaction flask. A fresh lot of tetrahydrof uran (10 ml)
was immediately added to cover the sodium hydride. To this
mixture was added a solution of 1,4-butanediol (0.9 gm, 10 mmolar
parts by weight) in tetrahydrof uran (10 ml by volume) over
a period of 15 min from a pressure equalizer duly protected
from the atmospheric moisture with the help of a calcium chloride
packed guard tube. The resulting mixture was stirred for 4
hrs at the refluxing temperature of tetrahydrofuran. It was
then cooled to 0-5ºC To this cold solution was added dropwise
over a period of ½ hr, a solution of methylaminosulfonyl chloride
(3.12 gm, 24 mmolar parts by weight) in dry tetrahydrof uran
(6 ml). After stirring at 0-5 C for 4 hrs/ the reaction mixture
was warmed to 60-65 C and kept at this temperature for 2 hrs.
The resulting mixture was allowed to stand in the freeze overnight.
Next day it was filtered under suction to remove the inorganic
salt which was washed twice with tetrahydrof uran (5 ml x 2).
Tetrahydrofuran was removed under reduced pressure in a rota-
vac to furnish an oily residue. The crude product was re-dissolved
in ethyl acetate (40 ml) and was transferred to a seperating
funnel. The organic layer was washed with brine (5 ml) and
worked up as usual. After the removal of ethyl acetate, the
weight of the crude oily product was 1.9 gm. This was subjected
to the column chromatography as usual by passing through
a column of silica gel (40 gm). The pure compound was obtained
as a white solid following crystallisation as described in
method A. Total yield was 0.85 gm.(30.8%).
In a similar fashion other compounds (n = 3/ 5-8) we're prepared
(General structure 1) following above methods.
WE CLAIM:
1. A one step process for preparing a compound of formula I

comprising treating the alkane diols of formula II

with methylaminosulfonyl chloride containing methylaminosulfonate group at a
temperature range of-10 to 30°c in the presence of a base selected from triethylamine,
potassium carbonate and sodium hydride in a suitable solvent
2. A process as claimed in claim 1, wherein the preferred temperature range is 0-5°C.
3. A process as claimed in claim 1, wherein the solvent used are ethyl acetate and
tetrahydrofuran (THF),
4. A process as claimed in claiml, wherein the solvent used is THF the base is
sodium hydride.
5. The compound dimethylanunosulibnates of alkane diols of formula I

A one step process for preparing a compound of formula I
comprising treating the alkane diols of formula II with methylaminosulfonyl chloride containing methylaminosulfonate group at a
temperature range of-10 to 30°c in the presence of a base selected from triethylamine,
potassium carbonate and sodium hydride in a suitable solvent.

Documents:

404-cal-1996-abstract.pdf

404-cal-1996-claims.pdf

404-cal-1996-correspondence.pdf

404-cal-1996-description (complete).pdf

404-cal-1996-examination report.pdf

404-cal-1996-form 1.pdf

404-cal-1996-form 18.pdf

404-cal-1996-form 2.pdf

404-cal-1996-form 3.pdf

404-cal-1996-granted-abstract.pdf

404-cal-1996-granted-claims.pdf

404-cal-1996-granted-correspondence.pdf

404-cal-1996-granted-description (complete).pdf

404-cal-1996-granted-examination report.pdf

404-cal-1996-granted-form 1.pdf

404-cal-1996-granted-form 18.pdf

404-cal-1996-granted-form 2.pdf

404-cal-1996-granted-form 3.pdf

404-cal-1996-granted-pa.pdf

404-cal-1996-granted-reply to examination report.pdf

404-cal-1996-granted-specification.pdf

404-cal-1996-pa.pdf

404-cal-1996-reply to examination report.pdf

404-cal-1996-specification.pdf


Patent Number 235851
Indian Patent Application Number 404/CAL/1996
PG Journal Number 36/2009
Publication Date 04-Sep-2009
Grant Date 02-Sep-2009
Date of Filing 04-Mar-1996
Name of Patentee CHITTARANJAN NATIONAL CANCER INSTITUTE
Applicant Address 37, S P MUKHERJEE ROAD, CALCUTTA
Inventors:
# Inventor's Name Inventor's Address
1 RANI PRAVA C/O CHITTARANJAN NATIONAL CANCER INSTITUTE, DEPT OF CHEMOTHERAPY, 37, S P MUKHERJEE ROAD, CALCUTTA 700 026
2 DR. UTPAL SANYAL C/O CHITTARANJAN NATIONAL CANCER INSTITUTE, DEPT OF CHEMOTHERAPY, 37, S P MUKHERJEE ROAD, CALCUTTA 700 026
3 MS. RANI PRAVA C/O CHITTARANJAN NATIONAL CANCER INSTITUTE, DEPT OF CHEMOTHERAPY, 37, S P MUKHERJEE ROAD, CALCUTTA 700 026
4 DR. UTPAL SANYAL C/O CHITTARANJAN NATIONAL CANCER INSTITUTE, DEPT OF CHEMOTHERAPY, 37, S P MUKHERJEE ROAD, CALCUTTA 700 026
5 MS. RANI PRAVA C/O CHITTARANJAN NATIONAL CANCER INSTITUTE, DEPT OF CHEMOTHERAPY, 37, S P MUKHERJEE ROAD, CALCUTTA 700 026
6 RANI PRAVA C/O CHITTARANJAN NATIONAL CANCER INSTITUTE, DEPT OF CHEMOTHERAPY, 37, S P MUKHERJEE ROAD, CALCUTTA 700 026
PCT International Classification Number C07D 307
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA