ZA200200158B - Process for producing dibenzothiazepine derivatives. - Google Patents
Process for producing dibenzothiazepine derivatives. Download PDFInfo
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- ZA200200158B ZA200200158B ZA200200158A ZA200200158A ZA200200158B ZA 200200158 B ZA200200158 B ZA 200200158B ZA 200200158 A ZA200200158 A ZA 200200158A ZA 200200158 A ZA200200158 A ZA 200200158A ZA 200200158 B ZA200200158 B ZA 200200158B
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- South Africa
- Prior art keywords
- derivative
- group
- carboxy
- diphenylsulfide
- formula
- Prior art date
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- 150000008509 dibenzothiazepines Chemical class 0.000 title claims description 23
- 238000000034 method Methods 0.000 title claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 150000001875 compounds Chemical class 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 238000006482 condensation reaction Methods 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 150000005181 nitrobenzenes Chemical class 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- NBOMNTLFRHMDEZ-UHFFFAOYSA-N thiosalicylic acid Chemical class OC(=O)C1=CC=CC=C1S NBOMNTLFRHMDEZ-UHFFFAOYSA-N 0.000 claims description 4
- 229910000564 Raney nickel Inorganic materials 0.000 claims description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 claims description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 3
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 claims description 3
- 238000006243 chemical reaction Methods 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 235000013350 formula milk Nutrition 0.000 claims 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims 4
- 239000003960 organic solvent Substances 0.000 claims 3
- 239000007868 Raney catalyst Substances 0.000 claims 2
- 229910052763 palladium Inorganic materials 0.000 claims 2
- 150000002941 palladium compounds Chemical class 0.000 claims 2
- 229910052697 platinum Inorganic materials 0.000 claims 2
- 150000003058 platinum compounds Chemical class 0.000 claims 2
- -1 2-hydroxyethoxy Chemical group 0.000 description 24
- 125000001424 substituent group Chemical group 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 230000000561 anti-psychotic effect Effects 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- YAZBBWJDISBOAL-UHFFFAOYSA-N benzo[d][1,2]benzothiazepine Chemical class S1N=CC2=CC=CC=C2C2=CC=CC=C12 YAZBBWJDISBOAL-UHFFFAOYSA-N 0.000 description 2
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- HUTXVUPGARJNHM-UHFFFAOYSA-N 1-(2-chloroethoxy)ethanol Chemical compound CC(O)OCCCl HUTXVUPGARJNHM-UHFFFAOYSA-N 0.000 description 1
- RMNTUOAOPRWVLP-UHFFFAOYSA-N 2-(2-aminophenyl)sulfanylbenzoic acid Chemical compound NC1=CC=CC=C1SC1=CC=CC=C1C(O)=O RMNTUOAOPRWVLP-UHFFFAOYSA-N 0.000 description 1
- RROSHIIMNNWHFW-UHFFFAOYSA-N 2-(2-aminophenyl)sulfanylbenzonitrile Chemical compound NC1=CC=CC=C1SC1=CC=CC=C1C#N RROSHIIMNNWHFW-UHFFFAOYSA-N 0.000 description 1
- VRVRGVPWCUEOGV-UHFFFAOYSA-N 2-aminothiophenol Chemical compound NC1=CC=CC=C1S VRVRGVPWCUEOGV-UHFFFAOYSA-N 0.000 description 1
- GDHXJNRAJRCGMX-UHFFFAOYSA-N 2-fluorobenzonitrile Chemical compound FC1=CC=CC=C1C#N GDHXJNRAJRCGMX-UHFFFAOYSA-N 0.000 description 1
- QZUQIMASXWGRRV-UHFFFAOYSA-N 5-iodo-5-nitrocyclohexa-1,3-diene Chemical class IC1(CC=CC=C1)[N+](=O)[O-] QZUQIMASXWGRRV-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000003891 ferrous sulphate Nutrition 0.000 description 1
- 239000011790 ferrous sulphate Substances 0.000 description 1
- 125000005446 heptyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- BAQGCWNPCFABAY-UHFFFAOYSA-N methyl 2-sulfanylbenzoate Chemical class COC(=O)C1=CC=CC=C1S BAQGCWNPCFABAY-UHFFFAOYSA-N 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005447 octyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 229960002195 perazine Drugs 0.000 description 1
- FWULFEHVLSQUBD-UHFFFAOYSA-N phenyl n-(2-phenylsulfanylphenyl)carbamate Chemical compound C=1C=CC=CC=1OC(=O)NC1=CC=CC=C1SC1=CC=CC=C1 FWULFEHVLSQUBD-UHFFFAOYSA-N 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229940103494 thiosalicylic acid Drugs 0.000 description 1
Landscapes
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
®
SPECIFICATION
PROCESS FOR PREPARING DIBENZOTHIAZEPINE DERIVATIVES
The present invention relates to a process for pre- paring a dibenzothiazepine derivative of value as an in- termediate compound for the preparation of pharmaceuti- cals. In particular, the invention relates to a process for the preparation of a dibenzothiazepine derivative of the following formula (5): oo 1 Oo . RY an RS “Y ) UY
R¥ S RS
R4 RS (5) (in which each of R', R?, R?}, R%? R® R% R’ and R® is the same or different from each other, and represents a hy- drogen atom, an alkyl group, an alkoxy group, an alkyl- carbonyl group, an aryl group, an aryloxy group, or an arylcarbonyl group, each group being optionally substi- tuted) which is of value as an intermediate compound for preparing 11-[4-(2- (2-hydroxyethoxy) ethyl] -1-piperadinyl- dibenzothiazepine and its derivatives, which is known to be effective as an antipsychotic pharmaceutical. | . [Background of Invention]
EP 0282236-A1 describes that a dibenzothiazepine derivative of the above-mentioned formula (5) can be pro- cessed to give 11-[4-(2- (2-hydroxyethoxy)ethyl] -1-pipera- dinyldibenzothiazepine derivative which is of value as an antipsychotic pharmaceutical. In more detail, dibenzo-
® [b, f] [1,4] thiazepin-11-one, which is a representative compound of the dibenzothiazepine derivatives of the formula (5), is reacted with phosphorus oxychloride to yield a ll-chloro-dibenzothiazepine derivative; and to the ll-chloro-dibenzothiazepine derivative is added pi- perazine to yield a ll-piperazinyl-dibenzothiazepine d- erivative, which is subsequently reacted with 2-chloro- ethoxyethanol under basic conditions to give the desired 11- [4- (2- (2-hydroxyethoxy) ethyl] -1-piperadinyldibenzo- thiazepin.
EP 0282236-A1 further describes that the dibenzo- [b,£f] [1,4] thiazepin-11-one is prepared from phenyl 2- (phenylthio) phenylcarbamate or its analogous compound by cyclization in the presence of polyphosphoric acid.
Helv. Chim. Acta., vol.42, pp.1263 (1959) describes that a dibenzothiazepine derivative can be prepared by the steps of heating a methyl thiosalicylate derivative with a 2-halogenated nitrobenzene derivative in the pres- ence of sodium to give a 2-nitro-2'-carboxy-diphenyl- sulfide derivative, which is then reduced using a Raney- nickel catalyst to yield a 2-amino-2'-carboxy-diphenyl- sulfide derivative, which is finally heated to give a dibenzothiazepine derivative.
Org. Prep. Proced. Int., pp. 287 (1974) describes that a dibenzothiazepine derivative can be prepared by the steps of heating a thiosalicylic acid ester deriva- tive and 2-iodo-nitrobenzene derivative in the presence of sodium methylate and copper, treating the resulting compound successively with an alkaline solution and an acidic solution to give a 2-nitro-2'-carboxy-diphenyl- sulfide derivative, reducing the derivative by ferrous sulfate in an aqueous ammonia solution to give a 2-amino- 2'-carboxy-diphenylsulfide derivative, and heating the resulting derivative under reduced pressure.
WO 92/19607 describes that a dibenzothiazepine de- rivative of the formula (5) can be prepared by the steps
® of reacting 2-aminothiophenol with 2-fluorobenzonitrile to give 2- (2-aminophenylthio)benzonitrile, hydrolyzing the resultant to give 2-(2-carboxyphenylthio)aniline, and finally cyclizing the aniline derivative.
As described above, various processes for preparing a dibenzothiazepine derivative of the formula (5) are known. However, the known preparing processes have vari- ous disadvantageous features such as a low yield, high temperature reaction conditions, use of starting com- pounds which are not easily available, and/or complicated post treatment. These disadvantageous features are natu- rally unfavorable in the industrial preparation of the - desired dibenzothiazepine derivative. - [Disclosure of Invention]
It is an object of the present invention to provide a process for industrially preparing a dibenzothiazepine derivative of the formula (5), that is, a process for preparing a dibenzothiazepine derivative in a good yield _ 20 without complicated post treatment, employing easily available material.
As the result of the earnest study of the present inventors, they have found a novel process for preparing a dibenzothiazepine derivative of the formula (5) in a good yield with easy operation by employing an easily available nitrobenzene derivative as well as an easily available thiosalicylic acid derivative. : The invention resides in a process for preparing a dibenzothiazepine derivative of the following formula (5): ]! OQ ge
H 7 2 R
R a8 oy
R”. Re RS in which each of R!}, R?, R?}, R%, R5, R%, R’ and R® indepen- dently represents a hydrogen atom, an alkyl group, an alkoxy group, an alkylcarbonyl group, an aryl group, an aryloxy group, or an arylcarbonyl group, each group being optionally substituted, which comprises the steps of: reacting a nitrobenzene derivative of the following formula (1):
NO,
R X r2 RO rR? (1) in which each of R!, R?, R® and R! has the meaning as described above, and X represents a halogen atom, with a thiosalicylic acid derivative of the following formula (2): ]
CO2H
HS R®
RS rR’
Cle
R (2) in which each of R®, R%, R’ and R® has the meaning as described above, to obtain a 2-nitro-2'-carboxy-diphenylsulfide derivative of the following formula (3): :
NO, COOH
RY S RS
R? R* RS R’
R® R®
® in which each of R!, R?, R3}, RY R®, Rf R’ and R® has the meaning as described above; reducing the obtained 2-nitro-2'-carboxy-diphenyl- sulfide derivative to obtain a 2-amino-2'-carboxy-di- phenylsulfide derivative of the following formula (4):
NH, COOH
RIC S R8 rR R® (4) in which each of R!, R?, R?}, R% R°% RS R’ and R® has the ) meaning as described above; and subjecting the obtained 2-amino-2'-carboxy-diphenyl- sulfide derivative to dehydration-condensation reaction.
The invention further resides in a process for pre- paring a dibenzothiazepine derivative of the formula (5):
RT HN a R®
R?
R7 ne ®at
R* RS R® (s) in which each of R}, R?, R?}, R*, R®, R°, R’ and R® has the meaning as described above, which comprises the steps of: reducing a 2-nitro-2'-carboxy-diphenylsulfide deriv- ative of the following formula (3):
NO, CO,H
R1 S RS
R2 R* RS R7
R3 R® (3) in which each of R!, R?, R3}, R* RS Rf R’ and R® indepen- dently represents a hydrogen atom, an alkyl group, an alkoxy group, an alkylcarbonyl group, an aryl group, an aryloxy group, or an arylcarbonyl group, each group being optionally substituted, to obtain a 2-amino-2'-carboxy-diphenylsulfide derivative of the following formula (4):
RI s 2
R
2
R R4 RS rR?
R3 8
R (4) in which each of R!, RZ, R}, RY RS, RS R’ and R® has the meaning as described above; and subjecting the obtained 2-amino-2'-carboxy-diphenyl- sulfide derivative to dehydration-condensation reaction.
The present invention further resides in a 2-nitro- 2'-carboxy-diphenylsulfide derivative of the formula (3).
The steps of the process for preparing a dibenzo- thiazepine derivative of the formula (5) according to the invention is illustrated by the following scheme:
NO, CO,H
R X HS RE in STEP-1 : 2
R R* RS UY
R 8 0 R 1 (1) (2)
NO, O,H
R! S 8
R STEP-2 —_— is 2 pe n7 REDUCTION 3 8
R (a) R
NH, COH
R! S Ré
STEP-3 ——————
R2 RRS r7 DEHYDRATION CONDENSATION 3 8
R™ (4) R o
Ri ] 8
HN R
R2 R’
S
R3 8
To Ld ds R (s)
In the formulas of the compounds involved in the process of the invention, "an alkyl group possibly having substituent" represented by R' through R® means a straight chain or branched chain alkyl group of 1 to 10 carbon atoms having no substituent, or a straight chain or branched chain alkyl group of 1 to 10 carbon atoms having substituent.
The above "straight chain or branched chain alkyl group of 1 to 10 carbon atoms having no substituent" preferably is a straight chain or branched chain alkyl group having 1 to 8 carbon atoms, more preferably 1 to 5 - carbon atoms. Examples of the alkyl groups include meth- vl, ethyl, propyl (including isomers), butyl (including isomers), pentyl (including isomers), hexyl (including isomers), heptyl (including isomers), octyl (including isomers), nonyl (including isomers), and decyl (including isomers). Preferred are methyl, ethyl, propyl (including isomers), butyl (including isomers), pentyl (including isomers), hexyl (including isomers), heptyl (including isomers), and octyl (including isomers). Most preferred are methyl, ethyl, propyl (including isomers), butyl (including isomers), and pentyl (including isomers).
Examples of the alkyl moiety of the above "straight chain or branched chain alkyl group of 1 to 10 carbon : atoms having substituent" include alkyl groups described in the above formula (1).
The substituent of the above-mentioned "straight chain or branched chain alkyl group of 1 to 10 carbon atoms having substituent" may be attached to any position of the alkyl moiety. Examples of the substituents in- clude straight chain or branched chain alkoxy groups having 1 to 10 carbon atoms such as methoxy, ethoxy, propoxy (including isomers), butoxy (including isomers), pentyloxy (including isomers), hexyloxy (including iso- mers), heptyloxy (including isomers), octyloxy (including
Claims (11)
1. A process for preparing a dibenzothiazepine derivative of the following formula (5): QO Ls R! R HN *~ ) R S R* 4 5 R® R R (5) in which each of R*, R?}, R?} R* R’, R° R’ and R® indepen- dently represents a hydrogen atom, an alkyl group, an alkoxy group, an alkylcarbonyl group, an aryl group, an aryloxy group, or an arylcarbonyl group, each group being optionally substituted, which comprises the steps of: reacting a nitrobenzene derivative of the following formula (1):
20. NO, R! X R? R* R3 (1) in which each of R!, R?, R® and R* has the meaning as described above, and X represents a halogen atom, with a thiosalicylic acid derivative of the following formula (2): oo CO2H ’ HS RS RS R7 - RS
@. in which each of R®, R®, R’ and R® has the meaning as described above, to obtain a 2-nitro-2'-carboxy-diphenylsulfide derivative of the following formula (3): > , NO CO,H R S ] R JOC XX R3 RO (3) in which each of R}, R?, R?®, RY R5, R% R’ and R® has the meaning as described above; _ reducing the obtained 2-nitro-2'-carboxy-diphenyl- sulfide derivative, to obtain a 2-amino-2'-carboxy- diphenylsulfide derivative of the following formula (4): NH, COH R! S R®
. § . ; § R® R® (4) in which each of R}, R?}, R3}, RY R% Rf R’ and R® has the meaning as described above; and subjecting the obtained 2-amino-2'-carboxy-diphenyl- sulfide derivative to dehydration-condensation reaction.
2. The process for the preparation of the dibenzo- thiazepine derivative as defined in claim 1, wherein the reaction between the nitrobenzene derivative of the for- mula (1) and the thiosalicylic acid derivative of the formula (2) is performed in an organic solvent in the presence of a base.
: 3. The process for the preparation of the dibenzo- thiazepine derivative as defined in claim 1, wherein the reduction of the 2-nitro-2'-carboxy-diphenylsulfide de- rivative of the formula (3) is performed in the presence 5S of a compound selected from the group consisting of Raney-nickel, a ferrous salt, palladium, platinum, a pal- ladium compound and a platinum compound.
4. The process for the preparation of the dibenzo- thiazepine derivative as defined in claim 1, wherein the dehydration-condensation reaction of the 2-amino-2'- carboxy-diphenylsulfide derivative of the formula (4) is performed in an organic solvent.
5. A process for preparing a dibenzothiazepine derivative of the following formula (5): 0 os R! R : HN R2 R’ R R* R® (5) in which each of R!}, R?, R3}, R* R®, R% R’ and R® indepen- dently represents a hydrogen atom, an alkyl group, an alkoxy group, an alkylcarbonyl group, an aryl group, an aryloxy group, or an arylcarbonyl group, each group being h optionally substituted, which comprises the steps of: reducing a 2-nitro-2'-carboxy-diphenylsulfide deriv- ative of the following formula (3): NO, CO4H Rr! S RS R? R* RS R’ R® R®
@. in which each of R!}, R?, R?, R%* RS, R% R’ and R® has the meaning as described above, to obtain a 2-amino-2'-carboxy-diphenylsulfide derivative of the following formula (4): RIC S RE R3 RS : (4) in which each of R}, R2?, R?}, R%* R5, Rf R’ and R® has the meaning as described above; and subjecting the obtained 2-amino-2'-carboxy-diphenyl- sulfide derivative to dehydration-condensation reaction.
6. The process for the preparation of the dibenzo- thiazepine derivative as defined in claim 5, wherein the reduction of the 2-nitro-2'-carboxy-diphenylsulfide de- rivative of the formula (3) is performed in the presence of a compound selected from the group consisting of Raney-nickel, a ferrous salt, palladium, platinum, a pal- ladium compound and a platinum compound.
7. The process for the preparation of the dibenzo- thiazepine derivative as defined in claim 5, wherein the dehydration-condensation reaction of the 2-amino-2'- carboxy-diphenylsulfide derivative of the formula (4) is performed in an organic solvent.
8. A 2-nitro-2'-carboxy-diphenylsulfide derivative of the formula (3):
) P. PCT/JP99/03719 NO, CO,H R? S 8 R 2 455 R ] RRS R7 8 R (ay R in which each of R!, R2, R3, RY, R%, R¢ R’ and R® independently represents a hydrogen atom, an alkyl group, an alkoxy group, an alkylcarbonyl group, an aryl group, an aryloxy group, Or an arylcarbonyl group, each group being optionally substituted.
9. A process according to claim 1 or claim 5, substantially as herein described and illustrated.
10. A derivative according to claim 8, substantially and herein described and illustrated.
11. A new process for preparing a derivative, or a new derivative, substantially as herein described. AMENDED SHEET
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ZA200200158A ZA200200158B (en) | 2002-01-08 | 2002-01-08 | Process for producing dibenzothiazepine derivatives. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ZA200200158A ZA200200158B (en) | 2002-01-08 | 2002-01-08 | Process for producing dibenzothiazepine derivatives. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200200158B true ZA200200158B (en) | 2003-09-23 |
Family
ID=30444539
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200200158A ZA200200158B (en) | 2002-01-08 | 2002-01-08 | Process for producing dibenzothiazepine derivatives. |
Country Status (1)
| Country | Link |
|---|---|
| ZA (1) | ZA200200158B (en) |
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2002
- 2002-01-08 ZA ZA200200158A patent/ZA200200158B/en unknown
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