CS242855B2 - Method of indanyle derivatives production - Google Patents

Abstract

Aryloxy-alkylsulphonylaminoindane derivs. and arylthio analogues of formula (I) are new (where Ar is phenyl or pyridyl each opt. substd. by halogen, CF3 or 1-4C alkyl; X is O or S; R1 is 1-4C alkyl opt. substd. by F or Cl; A1 is (CH2)3, CH=CHCH2, CYCH2CH2, CHZCH2CH2, CYCH(SOnR2)CH2 or CHZCH(SOnR2)CH2; Y is O, NOH, 1-4C alkoxyimino, phenylhydrazono or toluene-p-sulphonylhydrazono; Z is OH, 1-6C acyloxy, R1SO3, NH2, 1-6C acylamino, R1SO2NH or CN; n is 0-2; R2 is 1-4C alkyl, or Ph opt. substd. by halogen, 1-4C alkyl, NO2 or COOH; V is H, 1-6C acyl or R1SO2. The -CY- or -CHZ- gp. or -CH2- of CH=CHCH2 are either in the m- or p-posn. to ArX. (I) are herbicides and have analgesic, antipyretic, diuetic, thrombocyte aggregation-inhibiting and antiphlogistic activities; there is a great difference between therapeutic activity and undesirable side effects, esp. ulcerogenic activity, and they hardly inhibit prostaglandin synthesis.

Description

The invention relates to a process for the preparation of novel indanyl derivatives of the general formula (I).

AR -X

RSOjjNV

where

AR is phenyl,

X stands for oxygen atoe or sulfur atom,

In znamoeiá atoe atom, an acyl group having 1 to 6 e ^ t ^ ^ l ^ ernyuS Cart or sUppiuu formula ^R 1 ^S0 2 ~ '

R-C represents an alkyl group having from 1 to 4 carbon atoms, which is in contrast to fluorine or chlorine, and

A is a moiety of the formula -COCH 3 CH 3, and their salts with physiologically acceptable bases or salts. Pharmaceutical compositions containing these as active ingredient are described herein.

The individual derivatives of the general formula (I) are as subsititurit AR according to the invention.

For example, the substitution of the indanyl derivatives of the formula I is to be understood as being an oily, ethyl, polyl, isopropyl, buff, chloro, fluoromethyl or trifluoromethyl radical.

The indanyl derivatives of the formula (I) according to the invention are herbicides and pharmacologically active substances which are characterized by an analgesic, antipyretic, anti-platelet, diurnitis and, in particular, inflammatory action. In particular, the advantage of these compounds is justified by the fact that they find a large distribution due to the therapeutic effect and the undesirable side effect (especially the ulcer effect). Moreover, it is remarkable that these compounds barely interfere with the synthesis of prostaglandins

The intrinsic effect of the compounds of the invention can be determined by the known induction-arthhitis test, which is carried out as follows:

Male and male Lewis (LEW) rats were killed at a rate of 110-190 g. The animals were given drinking water and an atonine feed according to the drinking water.

• Dessei rats are used for each dose group.

As an irritant, MycoOsateriue blythyl is used. A 0.5 mg Myrcobaterial suspension in 0.1 ml of thin paraffin (DAB7) is injected into the right hindpaw. ·

The test substance is administered orally from day 11 on a daily basis for 4 days. It is administered as a clear aqueous solution or as a crystalline suspension with the addition of Myri 53 (85 mg%). in isitontene solution of sodium chloride.

Try

Rats are divided into different groups as far as possible with respect to their body rank. After the fullsolar gravity measurement of the right hind paw volume, the adjuvanted 0.1 Sil adjuvant was injected.

The right hind paw points from the fourteenth day of the experiment to its end. Duration of the experiment render 3 weeks. The extent of healing of the posterior taapas at a given dose is determined.

Frequent complications in therapy with non-steroidal suppression of inflammation appear as gastric ulcers. This side effect can be demonstrated in an animal test, whereby the number of lesions observed is determined for a given dose and their total area is examined. The ulcer test is performed as follows:

Male Wistar rats (SPF) are used in the test, with animals having a mass of 130 + 10 g: 16 hours prior to the start of the test, the animals stop feeding, but receive water ad libitum.

5 animals are used per dose. The compound is administered once orally, dissolved in sodium chloride or as a crystalline suspension with the addition of 85 mg% Myyi 53.

Three hours after administration of the substance, 1 ml of a 3% dye-oilyl dye solution was injected by intravenous injection and the animals were sacrificed. The stomach is removed and microscopic examination of the number and overall size of epptalations and ulcers that have appeared by administration of the dye.

The following table shows the results obtained in these tests on the compounds of the invention as compared to the known indomethacin (Compound 1).

From these results, the predominance of the compounds of the invention is apparent - particularly in view of their prevalence of distribution of the primary inflammatory effect and ulcerative effect.

Table

Ref . Substance Arrhhřtis Test iředovitovSi Substance in mg / kg animal Adjuvant test% right spot Damage Number Flat healing of the left tube Substance in mg / kg animal 1 inOorreacin 4x4 mg 50 70 8 9.6 6.3 2 N- (6-phenoxy-5-ynyl) -. ' reeannsUfvn- amide 4 x 30 mg 54 74 200 0.4 0.2 3 N- (6-Phenoxy-5-1-pentyl-1-trifluoromethanesulfone) LriO 4 x 30 mg 47 81 200 0.4 0.2 4 N- (6-H-fluorophenoxy) -5-L-methyl-methanesulfonate 4 x 30 mg 53 76 200 0.2 0.1 5 N / 6- (4-chloro- phenoxy) -5- -indany! / netan- sulocmmU 4 x 30 mg 61 ‘ 86 ‘ 200 1.4 0.7 6 N- / 6- U-chloro- -2-m ^ e ^ 1.f ^ en- oxy) -5-1п01пу1 / - mBeaiinu ufon- amide 4 x 30 mg 48 57 200 0.2 0.1

Test vředooitosSi damage

Substance Number Area in mg / kg animal

Adjuvans Arthritis test% healing pravVPlapka left paw

Continuation table

Cis. Substance Substance in mg / kg of animal

7 N 2 -U-chloro- phenoxy) -5-indanyl / methane- sulfonlbiO - 4 x 30 mg 8 N- (6-phenyltrid-5-ynyl) methanesulfonabide 4 x 30 mg 9 N- / 6- (2-Soyltride) -5-1пО1Пп1 / me ^ ans ufonamid 4 x 30 mg 10 5- / β-13β-pyridin-6-yl (lxy-1-nnolanone) 4 x 30 mg 11 N- (5-l-phenoxy-6-piperidin) methanesulfonamide 4 x 30 mg 12 5-beeylsuufoпу11ьгпо-6-phenoxy · ^^ nylsuufinyl- 4 x 30 mg

72

75

71

69

80

78

200 0.2 0.1

200 2.0 1.0

200 0.4 0.2

200 0.2 0.1

200 0.3 0.1

200 0.1 0.1

The novel compounds are useful in combination with carriers customary in galenic fatigue for the treatment of, for example, acute and chronic acute and chronic asthma, neuuodoemitis, ironchial asthma, hay fever and the like.

The manufacture of special medicaments is carried out in a conventional manner by converting the active ingredient with suitable additives, carriers and flavoring agents into the desired dosage form, such as tablets, dragees, capsules, solutions, suspending agents and the like.

Especially suitable for oral use are tablets, dragees and capsules which contain, for example, 1 to 250 mg of active ingredient and 50 mg to 2 g of pharmacologically active carrier, e.g. lactose, ammose, mother, gelatin, magnesium stearic acid and the like, as well as conventional additives.

The novel indanyl derivatives of the formula I can be prepared according to methods known per se. Suitable production methods are carried out, for example, by oxidizing an indane derivative of the formula I wherein A is -C -CC ^C C C and the other substituents are as defined above.

Oxidation bblylendvých groups ddpřdiíolíií carbo ^^ in the group according to the invention can be carried out e.g. with m ^ n ^ ^^ gaaii potassium carbonate alkaickkém neutral or weakly acidic aqueous solution or using a solution of chromium trioxide in glacial kyssUně dctov ^{e p} s tl ^rl dt ^j a ^{d -10 d} about ¹¹⁰ ° C.

The starting compounds for the process according to the invention are known or can be prepared according to methods known per se.

The conditions under which these starting compounds can be synthesized are described in the case of selected representatives in the following embodiments.

The following examples serve to illustrate the process according to the invention.

He said a

12.1

18.4

Solution

- brlI / - 6-nitroindane, boil phenol with 200, evaporate in vacuo, shake three times with 1N sodium hydroxide and 1N acid each.

0.75 g of copper (I) chloride, 17.3 g of potassium carbonate and absolute pyridine were added for 3 hours under reflux and chloroform was added and the insoluble material was filtered off with suction.

a) and with a whip.

The mother liquor is evaporated and evaporated in vacuo. After íesttllci in vacuo to give 11.5 g of 5-πit.oo6 - eπlxxyiudarш on te ^p ture ¹⁶ 3 and boiling ^{from 165} ° C ^{/ 4} mbar. Melting point 41 ° C (liexane).

in you

(b) The flow of 17.7 g of ito-6-phenoxy-iodide in 500 ml of methanol is hydrogenated in a half-liter of Raney nickel for 4 hours under a pressure of 7.0 MPa. The catalyst was then filtered off, the solution was evaporated in vacuo and recrystallized from aqueous ethanol. 12.9 g of 6-hydroxy-indole are obtained at 62 ° C.

^p ou interior temperatures under 0 pi 0 ° <chloroform, shaken three times with 1N hydrochloric acid and odpaH in vacuo. recrystallized from te ^p] T ^and the OTE

c) To a solution of 7.8 g of 6-feπlxc --- indřπclaíinu in 50 ml of absolute pyridine PRIK · C ^h em It runs ¹⁰ minutes 4 ml niulf meth ^ (I ^ C ^ ^C ^ L ri ^{u. The} organic solution was ^{HA 3} MIC ¹ <^ ^1п с C. and 16 hours at temperatures produce místnooti and then concentrated in vacuo. the residue was taken up then aqueous ethanol to give 9.5 g of N- (6-fenlxc --- indancl) íetřπsuflxnaíid 130 Deň: 32 ° C.

he said and d

EXAMPLE 1 Example 1 is obtained from 5-bromo-6-nitroindane and 4-chlorophenol and proceeds analogously to

a) C ^- - ⁽⁴ -chllr enlxy ^{f) -6} -iitlO ídai ^and the boiling point ^{of 165 (hexann,} 168 ° C / 4

Pa ^ ^t e ^pl ^ ot ^ ^{E t} U ^s

(b)

6- ^{(4-chlorophenoxy-S-} ^ ddanyamin the heat ^of counting ^as 66 ° C,

C)

N / ⁶ - ^{(4-c h e} LOF nnox ^HS-yl-phenyl id / IEE NSU ^. ^ NNAME a lot ^{of p} te mp ° C.

Example of the laying

Vyccázi - i

1, is obtained from --brlm -> 6-nitroidium and p-cresol and proceeds analogously to that of yarn

a) ° C

5 - ^^ - ^ ⁽⁴ ^ -tol xy ') ^ gift of boiling temperature between approximately ¹⁶⁸ to ¹⁷³ ° C / ⁴ aa ^{beta t} Ar ^{I (h} Exan ^n'

(b)

6- (4-tolyloxy) -S-ídlanylamin as an oil, ^{c) N} / ^{6- (4-ol t} ^ ^L ^ ^l · xcy-- ^- j ^{π Π} ^ ^R πc ^{L 'i} ^ i ^ Gentle, ^IL n ^ R ^ ^fa ^ nd the tote on te ^th Ri 1 to ³⁹ ° C.

Example4

Extracted from the nitroindrone and 4-fluorophenol and proceeded analogously to Example 1 to give

a) 5- (4-fluorophenoxy) "6-nitroiddan of ^p te ture mp бр 4hexan ° C)

b) 6- ⁽⁴ ~ f ^1иог е епоху) -5- ^ 0апу! -amino te ^p LRT point ^{of 72} ° ^{C, N?} / ⁶ ~ ^(4- f lf R ^E phenoxy) ^^ ndanyl / methanesulphonamide nesulfonamide ^ te ^p lo ^{I th} the ¹⁰ ° C.

Example 1 and d 5

Extracted from 5-bromo-nitroindane and 3-trifluoromethyffenol and proceeded analogously to Example 1 to give

a) N-N, N-O-O-O-trifluoromethyl. ^y ^ ^e noox ddan on te ^p lo ^thee boiling point ^{of 15} 5 to ÍL63 ° C / ⁴ mbar and ^I lo ^p te ^ u 69 ° C ^(h Exan)

(b) 6- (3-Trifluoro-phenyleneoxy) -5-idannylamine in the form of an oil;

c) -5 ^{п 1пс1пуу г} / mt ^and nnsu ^fo NNAME ^p te ^d by Tian lot ^{of 8} 1 ° C.

Example 6

Starting from D-bromo-4-trifluorodane and 4-chloro-2-methylphenol and proceeding analogously to Example 1 to give

a) ⁵ · ⁽⁴ cl ^ ^hL or ^2- m ^et en ^ ^yl ^ x ^{χ ')} - 6- ^ ^ l ^ ^i. 1 ^t ^ o ^ N ^ C ^ n of te ^P1 about ^the boiling point of 1.87 and ^{Z 19} 0 C / 4 mbar and OT TE ^{p1 of} the 6 ^{T 1} ° C (hexane)

(b) 6- (4-chloro-2-methylphenoxy) -5-idanyl-amine as an oil;

c) N- [6- (4-chloro-2-methyphenoxy) 55-indinyl] -methanesulfonamide, m.p. 116 [deg.] C.

Example 7.

Starting from 5-bromo-66-nitronanedane and 2-chloroform, and proceeding analogously to Example 1, one obtained

a) ⁵ - ^{(2-chloro-phenoxy)} - ^6-nitro ndin ⁿ of te rt ^pl I ^of boiling ⁷⁵ and ^Z and ⁷⁸ ° C / ^{4 mbar,}

(b) 6- (2-Calorphenoxy) -5-indanylamine in the form of an oil;

c) N / 6- ⁽² -c ^h LOF nnoxy ^{e) 5} - d ^{i and} nnyl / ^f0 meannsu NNAME ^into te rt ^{pl of} the T ^and 120 ° C.

Example ⁸ ,

Starting from 5-bromo-3-nitro-indane and 3-caloropheno11 and proceeding analogously to Example 1, one obtains:

a) ⁵ - ^{(3-chloro-phenoxy)} - ^6-nitro ndin ⁿ of te ^ OTE I boiling ⁷⁶ and ¹⁸² ° C / ⁴ mbar,

(b) 6- (3-chlorophenoxy) -5-idanyl-amine as an oil;

c) N / ⁶ - ⁽³ -c ^h0 Of nnoxy ^e) 5 ^- - ⁱ d ^and ndyl / meannsul ^of Naam ⁱ to ^t ^ e ^pl ^ ot ^ u ^{of 109} and ¹¹¹ ° C.

Example 9

Starting from 5-bromo-6-nitroindan and 2-fluorophenol and proceeding analogously to Example 1,

(a) 5- (2-fluorophenoxy) -6-nitroindane, boiling point 155 to 165 ° C / 4 Pa and melting point 47 ° C,

(b) 6- (2-fluorophenoxy) -5-indanylamine as an oil;

c) N- [6- (2-fluorophenoxy) -5-indanyl] methanesulfonamide, m.p. 78 [deg.] C.

Example 10

Starting from 5-bromo-6-nitroindan and 2-chloro-4-fluorophenol and proceeding analogously to Example 1, the following are obtained:

(a) 5- (2-chloro-4-fluorophenoxy) -6-nitroindane as an oil;

(b) 6- (2-chloro-4-fluorophenoxy) -5-indanylamine, m.p. 63 ° C;

c) N- [6- (2-chloro-4-fluorophenoxy) -5-indanyl] methanesulfonamide, m.p. 90 [deg.] C.

Example 11

Starting from 5-bromo-6-nitroindane and 3,4-dichlorophenol and proceeding analogously to Example 1, the following are obtained:

(a) 5- (3,4-dichlorophenoxy) -6-nitroindane, after purification on a silica gel column (tetrachloromethane: ethyl acetate-30 µl), as an oil, (

(b) 6- (3,4-dichlorophenoxy) -5-indanylamine, m.p. 84 ° C;

c) N- [6- (3,4-dichlorophenoxy) -5-indanyl] methanesulfonamide, m.p. 135 [deg.] C.

Example 12

Starting from 5-bromo-6-nitroindan and 4-bromophenol and proceeding analogously to Example 1, the following are obtained:

(a) 5- (4-bromophenoxy) -6-nitroindane, bp 183-185 ° C / 4 Pa;

(b) 6- (4-bromophenoxy) -5-indanylamine, m.p.

c) N- [6- (4-bromophenoxy) -5-indanyl] methanesulfonamide, m.p. 118 [deg.] C.

Example 13

Starting from 5-bromo-6-nitroindane and 2,4-dichlorophenol and proceeding analogously to Example 1, the following are obtained:

(a) 5- (2,4-dichlorophenoxy) -6-nitroindane, after purification in a silica gel column (tetrachloromethane: ethyl acetate -30: 1) as an oil;

(b) 6- (2,4-dichlorophenoxy) -5-indanylamine as an oil;

c) N- [6- (2,4-dichlorophenoxy) -5-indanyl] methanesulfonamide, m.p. 90 [deg.] C.

Example 14.

In bromo-nitroindine and o-cresol and proceeding analogously to Example 1, the following is obtained:

(a) - nitro-6H-tolyloxyidene with a boiling point of 163 to 166 ° C7 Pa;

b) 6- (2 H -tetol-10-ol-5-yl) -5-idadiazole-1-ol in petroleum oil, c ⁾ N- / ⁷ 6- ^{(2- t} ols oxyH ^O ^ ir ^ ny ¹⁾ methyl-NSU Onam ^ ^ o te ^pl of ^I T ^and the ⁹² ° C.

He said 15 ·

Vyycháí- / i from --brom 6-nitroindane-rlufrfeoflu and 3 and the same procedure as in příkaadu 1, yielding ^{a) -} - (3 luorfeoooy ^{r) / 6} / oito ^ te ^ dao about 155 to boil OTE 163 ° CL4 Pa, ^{b) 6} - ^(3-phenyl-S- ^ orfenoo little read ^ ^ min o te ^ ture ^{p tio n s 49} ° C, ^c) N / ⁶ - ⁽³ -f ^l oro OOOx ^f / - ^/ -. ⁱ ddaIΊy ^l / ^LF mftdrlSl Onami ^d of ^p te ture T ^and the ^two 10 ° C.

Example 16

(a) 14.6 g of bromo-66-nitroindole, 1.2 g of chloride, 12.4 ml of thiophenol and 8.4 g of potassium carbonate are refluxed in 150 ml of absolute pyridine for 3 hours. The solution was then evaporated in vacuo and the residue treated as described in Example 11a. Rekkrltadizací edylesteru of acetic acid, 8.1 g 5 / ^ le ^ i ^ o y.thi-6-ni ^t d ⁱ toi ^ C ^ ou ^^ OTE of the LL ^{T 2} ° C.

(b) To a solution of 9 g of ioylthif-6-oidf-ifane in 160 ml of ethanol and 6.6 ml of hydrazine hydrate is added 5 g of Raney nickel at boiling point and refluxed for 1.1 / 4 hours. The catalyst is then filtered off, lildrát odpaaí up to crystallize to yield 7.1 g of 6-phenyl-io-S ^^ ^ mine any of te ^ ^th the OTE ⁸⁰ ° C.

c) the product obtained is reacted as described in paíkaadu 11c to give N- (6-f ^--- ienylthi ^ ii ^ ^f ^ ⁱ ^ d ^l) MTI ^ i ^ s ^ s ^ ^{l. i} ^ f ^ from ^m . ^d a ^{p t} e l.ot ^th ^ of the ^ 115 ° C.

example 17

The product is volatilized from 5-bromo-10-tetraindda and 4-tert-butyldiophenol and proceeds analogously to Example 16, yielding:

a) - ⁽⁴ -tert eiylthif ⁱ⁾ -6-oitfo fddo ^and a ^p te ture point 94 DEG C. ^{b) 6} - ^(4-tert. utylfeo ^{b y} lth ^f o) ^- - f ^{i and} NNY dm ^t oo ⁱ te ^ OTE T ^and the ⁹² ° C,

c) N- [6- (4-tert-butylphenyl) -5H-indoyl] -one-sulfonamide, m.p. 116 [deg.] C.

Example 18

It is recovered from bromo-6-nitroindaou and 4-ilufrthiofeoflu and proceeds in a similar manner as in paqadaad 16 to obtain.

(a) 5- (4-fluorophenylthio) -6-nitroindane, m.p. 106 ° C;

b) 6- (4-fluorophenylthio) -5-indanylamine, m.p. 60 ° C;

c) N- [6- (4-fluorophenylthio) -5-indanyl] methanesulfonamide, m.p.

Example 19

(a) 2.4 g of 5-bromo-6-nitroindane, 2.25 g of potassium tert-butoxide and 2.9 g of 4-chlorothiophenol are heated in 30 ml of absolute dimethylformamide under nitrogen for 3 hours at 60 ° C. The solution was evaporated in vacuo, ethyl acetate was added and the mixture was shaken three times with 2N sodium hydroxide. The solution was evaporated again and the residue was purified on a silica gel column (carbon tetrachloride: ethyl acetate = 25: 1) and recrystallized from ethanol. 1.2 g of 5- (4-chlorophenylthio) -6-nitroindane of melting point 118 DEG C. are obtained.

b) 6- (4-Chloro-phenylthio) -5-indanylamine, m.p. 63 DEG C., was obtained in analogy to Example 16b.

c) Analogously to Example 1c, N- [6- (4-chlorophenylthio) -5-indanyl] methanesulfonamide, m.p. 109 [deg.] C., is obtained.

Example 20

(a) 4.8 g of 5-bromo-6-nitroindan, 4.5 g of potassium tert-butoxide and 4.4 g of 2-mercaptopyridine are heated in 80 ml of absolute dimethylformamide under nitrogen for 3 hours at 80 ° C. The solution is concentrated in vacuo, ethyl acetate is added to the residue and the mixture is shaken with water four times. The ethyl acetate phase was evaporated and the residue was purified on a silica gel column (cyclohexane: ethyl acetate = 4: 1). After recrystallization from ethanol, it is obtained

3.3 g of 5-nitro-6- (2-pyridylthio) indane, m.p. 74 ° C.

(b) 6- (2-Pyridylthio) -5-indanylamine, m.p.

c) N- [6- (2-Pyridylthio) -5-indanyl] methanesulfonamide, m.p. 141 [deg.] C., was obtained in analogy to Example 1c.

Example 21

a) 7.2 g of 5-bromo-nitroindan and 3.9 g of 4-mercaptopyridine were heated in 120 ml of dimethyl sulfoxide with 3.6 g of sodium bicarbonate at 50 ° C for 7 hours under nitrogen. The solution was evaporated and the residue dissolved in chloroform / water and shaken three times with water. It is again evaporated and purified on a silica gel column (cyclohexane: ethyl acetate = 1: 1). Recrystallization from ethanol gave 2 g of (5- (n-pyridylthio) -6-nitroindane), m.p. 113 ° C.

b) 6- (4-Pyridylthio) -5-indanylamine, m.p. 140 [deg.] C., was obtained in analogy to Example 16b.

c) N- [6- (4-Pyridylthio) -5-indanyl] methanesulfonamide, m.p. 156 [deg.] C., was obtained analogously to Example 1c.

Example 22

Starting from 5-bromo-6-nitroindane and 3-chloropyridine and proceeding analogously to Example 1, the following are obtained:

(a) 6- (3-chlorobenzoyl) -5-nitroanedane as an oil;

b) 6- (3-pyrid ^y l ^p> x ^r) - ⁵ - ^{n r} Daan laain the temperature Toni l ¹⁸ ° ^C,

c) N, N - (R) riclytox (R) - id (R) -1 / metholsul. toaamto of te ^pl ot ^{th of} the ¹²⁶ ° C.

Example 23

1.1 g of 6-5-ffnlxy indanraaa-NK were dissolved in 15 ml of dry pyridine at rt te ^{pl of} 0 ° C, ¹⁰ minutes Bétou ^P s ^{be 1.6} ml anhydride ^ sel:! ^ ^T ri ^for luoreeaanskl ^l NNL> OE in 5 ml of absolute benzene. The whole was stirred ^{for 3 h} Odin ^yp s ⁰ and s ¹⁶ tocdin ^p te ^pl Ote room odpaaí in vacuo, the residue taken up chlorooormem and extracted three times with 1N hydrochloric acid. The chloroform phase is then evaporated in vacuo, the residue is purified on a silica gel column (system: chloroform) and recrystallized with 2 hexanes. 0.74 g of N- ^{(6-ffnoxyr5-kl} indaanrltri uareeannsu ^fo INAMI ^d ko te ^pl OTE t ^N, the ⁹⁰ ° C..

Example 24

Vyhává--! from 6-0firlthio55-idaiaylariik and procedures as in Example 23 to give N - ^ - ^ mtoda phenylthio-l ^ ^ οι πο θtisкu ^ol iaari ^ ^d on this point ^{of 67} ° C.

Example 25

V ^ r ^ · ^ í CAZ-l- from 6- (4-fkuoreiaoxy) -5-ialanylamink and procedures as in Example 23 CIS Å ^to 7-N ⁶ - ^{(4-fluoro-phenoxy to r)} - ⁵ - ⁱ ndaiyl / fi ^{r and kl} roret issu ^{d 0 l} iaari TopFoto of the ^{T 123} ° C.

Example 26

VyrCází '- and from 4-chllreenlxr 5 - iddarlrlamink and procedures as in Example 23 to give the ^{N? / 6} - (4-C of ^N- lr ^f € ^ CE ^ ^{χ) -5} - ^ i ^ dai ^r ^ ^{rl / r} - ^'lкl rmetain' ^ u ^ol n ^ e ^ ^d m of this point ^{of 139} ° C.

Example 27

VyrCází "-i from 6-5-ffnlxr indanrlaminu and procedures as in Example 23 to obtain N- ⁽⁶ - ^{f fnlxy-5-yl} iadan) CH ^{l l} ormftantкl oaami ^d te ^pl of about ^thee foni ⁷³ ° C .

Example 28

VVycháí - even from 6-5-ffnlxr iadanrlam-nu and procedures as in Example 23 to give N- (6- ^f filxy 5-iiιíaiyl) ftantu ^the fon of te ^{s pl} ol tdní ^{of 89} ° C.

Example 29

a) 11 g of 5-nitoo6 - filox ^y iddlrш and 17.3 g of press-heated diretylarinnoterc.bktoxraetank ⁶ 0 minutes to a temperature of ¹⁵⁵ ° C for ⁶⁰ minutes and ^p s udrtoje this temperature, p ^r i ^{f f} e is tert oddeftilkje .lktaiol. The solution is then evaporated in vacuo, 50 [mu] l ethanol is added and the solid is filtered off with suction. 9.2 g · l-dimftrlarinlmefy reni55nitro ^6feilox-yl iddank mp 97 ° C.

b) 6.2 g of this woman are dissolved in 100 l of chloroform and from ^-35 ° C. After tolrraci ^BC EC ³⁰ g ^clay forces ^L to age using πίοο ^^ ^^ ^ scalding and tolfoace 30 Ol ethanol gave 3.8 g of 5-iitro-6ffenl> xr-l-iíainlnk m.p. 105 ° C.

c) 1.58 g of these isoocetoetics are dissolved in 20 [mu] l of ethanol and 10 ml of dioxane. The solution was mixed with 0.74 g and ^{y y} drlzinh wire portions including therein of about 1.5 g of Raney nickel (skspen ^d toanéht in ethanol) ^p s at ³⁵ ° C. After this reflux esátiainutovém ^{d p} s reflux the mixture was cooled, filtered and evaporated. Recrystallization from ethanol gave 1.22 g of 5-amino-6-phenoxy-1-indanone, m.p. 170 ° C.

d) 1.2 g of this aminoketone are evaporated under vacuum in 12 ml of pyridine at 0 DEG C., ice water is added to the residue and suction filtered. Dissolve the precipitate in dilute sodium hydroxide solution and acidify the filtered solution with hydrochloric acid. Extraction and recrystallization from ethanol gave 1.35 g of 5-methylsulfonylamino-6-phenoxy-1-indanone, m.p. 175 ° C.

Example 30

Analogous to Example 29, starting from 6- (4-chlorophenoxy) -5-nitroindane

(a) 6- (4-chlorophenoxy) -1-dimethylaminomethylene-5-nitroindane, m.p. 117 ° C;

(b) 6- (4-chlorophenoxy) -5-nitro-1-indanone, m.p.

(c) 5-amino-6- (4-chlorophenoxy) -1-indanone, m.p. 169 ° C;

d) 6- (4-chlorophenoxy) -5-methylsulfonylamino-1-indanone, m.p. 185 ° C.

Claims (1)

SUBJECT OF THE INVENTION A process for the preparation of indanyl derivatives of the general formula I wherein AR is phenyl, X represents an oxygen atom or a sulfur atom, V represents a hydrogen atom, an acyl group having 1 to 6 carbon atoms or a group of the formula r _{1 and 2} -, R 1 represents a C 1 -C 4 alkyl group optionally substituted by a fluorine or chlorine atom and A represents a group of the formula -COCH ₂ CH ₂ -, and their salts with physiologically acceptable bases or acids, characterized in that an indane derivative of the formula I is oxidized, wherein A represents a group -CH ₂ CH ₂ CH ₂ - and the other substituents have the above meaning.