This invention describes the new, nonsteroidal gestagens of general formula I ##STR1## in which A, B, Ar, R.sup.1, R.sup.2 and R.sup.3 have the meanings that are indicated in more detail in the description. The new compounds show a very great affinity to the gestagen receptor. They can be used alone or in combination with estrogens in contraceptive preparations. In addition, they can be used for treating endometriosis. Together with estrogens, they can also be used in preparations for treating gynecological disorders, for treating premenstrual symptoms and for substitution therapy. Based on the androgenic action, they can also be used for male birth control, male HRT and hormone therapy and for treating andrological disease agents.

This invention relates to nonsteroidal compounds, which have a high
 gestagenic activity.
 In addition to a large number of steroid compounds with gestagenic action,
 gestagens that are not steroids are also known (for example from EP 0 253
 500 B1 and WO 94/01412, cf. J. Med. Chem. 38 (1995) 4878).
 This invention describes the compounds of general formula I
 ##STR2##
 in which
 R.sup.1 and R.sup.2 are the same or different and stand for a hydrogen
 atom, a C.sub.1 -C.sub.5 alkyl group or a halogen atom, and also together
 with the C-atom of the chain stand for a ring with a total of 3-7 links,
 R.sup.3 stands for a C.sub.1 -C.sub.5 alkyl group or a partially or
 completely fluorinated C.sub.1 -C.sub.5 alkyl group,
 A stands for a monocyclic or bicyclic aromatic ring that is optionally
 substituted by one or more radicals, selected from halogen atoms, C.sub.1
 -C.sub.5 alkyl groups, C.sub.2 -C.sub.5 alkenyl groups
 --CR.sup.5.dbd.CR.sup.6 R.sup.7, whereby R.sup.5, R.sup.6 and R.sup.7 are
 the same or different and, independently of one another, mean hydrogen
 atoms or C.sub.1 -C.sub.5 alkyl groups; hydroxy groups, hydroxy groups
 that carry a C.sub.1 -C.sub.10 acyl group, a C.sub.3 -C.sub.10
 carbalkoxyalkyl group, a C.sub.2 -C.sub.5 cyanalkyl group, a C.sub.3
 -C.sub.10 unsubstituted or substituted allyl group, a C.sub.3 -C.sub.10
 unsubstituted or substituted propargyl group, a C.sub.2 -C.sub.5
 alkoxyalkyl group, a C.sub.1 -C.sub.5 alkyl group that is partially or
 completely substituted by fluorine atoms, the cyano or nitro group,
 C.sub.1 -C.sub.5 alkoxy groups, C.sub.1 -C.sub.5 alkylthio groups, mono-
 or disubstituted C.sub.1 -C.sub.10 amino groups or partially or completely
 fluorinated C.sub.1 -C.sub.5 alkyl groups, for an ester group
 --COOR.sup.4, whereby R.sup.4 means a C.sub.1 -C.sub.5 alkyl group, for a
 C.sub.2 -C.sub.5 alkenyl group --CR.sup.5.dbd.CR.sup.6 R.sup.7, whereby
 R.sup.5, R.sup.6 and R.sup.7 are the same or different, and, independently
 of one another, mean hydrogen atoms, halogen atoms, aryl radicals or
 C.sub.1 -C.sub.5 alkyl groups, for an alkinyl group --C.dbd.CR.sup.5,
 whereby R.sup.5 means a hydrogen atom or a C.sub.1 -C.sub.5 alkyl group,
 for a partially or completely fluorinated C.sub.1 -C.sub.5 alkyl group,
 B stands for a carbonyl group or a CH.sub.2 group, and
 Ar stands for a ring system, selected from the group of general partial
 formulas 2-11,
 ##STR3##
 ##STR4##
 in which
 radicals X.sup.3a, X.sup.4, X.sup.6, X.sup.7 (in partial formula 2),
 X.sup.4, X.sup.6, X.sup.7 (in partial formulas 3 and 4), X.sup.3a,
 X.sup.3b, X.sup.4, X.sup.6, X.sup.7 (in partial formulas 5, 6 and 7) or
 Y.sup.4, Y.sup.5, Y.sup.7, Y.sup.8 (in partial formulas 8, 9, 10 and 11)
 are the same or different and are selected from hydrogen atoms, C.sub.1
 -C.sub.5 alkyl groups, which in addition can contain a hydroxy group that
 is optionally etherified with a C.sub.1 -C.sub.5 alkyl group or esterified
 with a C.sub.1 -C.sub.5 alkanoyl group, partially or completely
 fluorinated C.sub.1 -C.sub.5 alkyl groups, C.sub.2 -C.sub.5 alkenyl groups
 --CR.sup.5.dbd.CR.sup.6 R.sup.7, whereby R.sup.5, R.sup.6, and R.sup.7
 have the above-mentioned meaning, alkinyl groups --C.dbd.CR.sup.5, whereby
 R.sup.5 has the above-mentioned meaning,
 radicals X.sup.3a and X.sup.3b also together with the C-atom of
 benzocondensed ring system 5, 6 or 7 can form a ring with a total of 3-7
 links,
 and moreover, radicals X.sup.4, X.sup.6, X.sup.7 (in partial formulas 2, 3,
 4, 5, 6 and 7) or Y.sup.4, Y.sup.5, Y.sup.7, Y.sup.8 (in partial formulas
 8, 9, 10 and 11) are selected from halogen atoms, hydroxy groups, C.sub.1
 -C.sub.5 alkoxy groups or C.sub.1 -C.sub.5 alkanoyloxy groups,
 also if B in general formula I stands for a CH.sub.2 group, Ar in addition
 stands for a phenyl radical of general partial formula 12,
 ##STR5##
 in which R.sup.9 and R.sup.10 are the same or different and mean a cyano
 group, a nitro group, a halogen atom, a C.sub.1 -C.sub.5 alkyl group, a
 C.sub.1 -C.sub.5 alkoxy group, a partially or completely fluorinated
 C.sub.1 -C.sub.5 alkyl group, a C.sub.1 -C.sub.5 alkylthio group, a
 C.sub.1 -C.sub.5 alkylsulfinyl group or a C.sub.1 -C.sub.5 alkylsulfonyl
 group, and if B stands for a CH.sub.2 group, the physiologically
 compatible salts of the compounds of general formula I with acids.
 The compounds according to the invention are distinguished from the known
 nonsteroidal compounds with gestagenic action by the substitution pattern
 on the aryl radical that is on the right in general formula I. In the
 compounds that are present here, Ar is a benzocondensed, bicyclic ring
 system, while in the structures that are known from EP 0 253 500 B1 and
 that can be considered as the closest compounds, a phenyl radical that is
 substituted in one, two or three places is at this point.
 The compounds of general formula I according to the invention can be
 present as different stereoisomers because of the presence of asymmetry
 centers. Both the racemates and the stereoisomers that are detached are
 part of the subject of this invention.
 The substituents that are defined as groups in the compounds of general
 formula I can have the following meanings in each case.
 C.sub.1 -C.sub.5 Alkyl groups can readily be a methyl, ethyl, n-propyl,
 isopropyl, n-, iso-, tert-butyl group or an n-pentyl, 2,2-dimethylpropyl
 or 3-methylbutyl group. A methyl or ethyl group is preferred.
 A fluorine, chlorine, bromine or iodine atom can stand for a halogen atom.
 Here, fluorine, chlorine or bromine is preferred.
 If R.sup.1 and R.sup.2 together with the C-atom of the chain form a
 3-7-membered ring, this is, for example, a cyclopropyl, cyclobutyl,
 cyclopentyl or cyclohexyl ring. The cyclopropyl ring is preferred.
 For a partially or completely fluorinated C.sub.1 -C.sub.5 alkyl group, the
 perfluorinated alkyl groups that appear above and of the latter mainly the
 trifluoromethyl group or pentafluoroethyl group as well as partially
 fluorinated alkyl groups, for example, the 5,5,5,4,4-pentafluoropentyl
 group or 5,5,5,4,4,3,3-heptafluoropentyl group are considered.
 As a C.sub.2 -C.sub.5 alkenyl group, for example, a vinyl-, allyl- or
 2,3-dimethyl-2-propenyl group can appear; if aromatic compound A is
 substituted with an alkenyl group, preferably it is a vinyl group.
 Representatives of a C.sub.1 -C.sub.5 alkoxy group are selected from
 methoxy, ethoxy, n-propoxy, iso-propoxy, n-, iso-, tert-butoxy groups or
 n-pentoxy, 2,2-dimethylpropoxy or 3-methylbutoxy groups. A methoxy or
 ethoxy group is preferred.
 C.sub.1 -C.sub.5 Perfluoroalkoxy groups are the corresponding
 perfluorinated radicals of the C.sub.1 -C.sub.5 alkoxy groups above.
 Monocyclic or bicyclic aromatic ring A, which can be substituted, is a
 carbocyclic or heterocyclic aryl radical.
 In the first case, this is, for example, a phenyl or naphthyl radical,
 preferably a phenyl radical.
 As a heterocyclic radical, for example, a monocyclic heterocyclic radical
 can be, for example, the thienyl, furyl, pyranyl, pyrrolyl, imidazolyl,
 pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thiazolyl,
 oxazolyl, furazanyl, pyrrolinyl, imidazolinyl, pyrazolinyl, thiazolinyl,
 triazolyl, tetrazolyl radical, specifically all possible isomers relative
 to the positions of the heteroatoms. The thienyl radical is preferred as
 heteroaryl radical A.
 For R.sup.4, a methyl, ethyl, n- or iso-propyl group is preferred as a
 C.sub.1 -C.sub.5 alkyl group in ester group --COOR.sup.4.
 As a C.sub.1 -C.sub.5 alkyl group for etherification of hydroxy groups, the
 above-mentioned alkyl groups are suitable, primarily a methyl or ethyl
 group.
 As a C.sub.1 -C.sub.5 alkanoyl group for esterification of hydroxy groups,
 a formyl, acetyl, propionyl, butyryl, isobutyl, valeryl or isovaleryl
 group is suitable, preferably an acetyl group.
 If X.sup.3a and X.sup.3b together with the C-atom of the benzocondensed
 ring system form a 3-7-membered ring, this is, for example, a cyclopropyl,
 cyclobutyl, cyclopentyl or cyclohexyl ring. The cyclopropyl ring is
 preferred.
 As a C.sub.1 -C.sub.5 alkanoyloxy group for X.sup.4, X.sup.6, X.sup.7,
 Y.sup.4, Y.sup.5, Y.sup.7 or Y.sup.8, a formyloxy, acetoxy, propinoyloxy,
 butyryloxy, iso-butyryloxy, valeryloxy or isovaleryloxy group is suitable,
 preferably an acetoxy group.
 The above-mentioned C.sub.1 -C.sub.5 alkyl groups can stand for C.sub.1
 -C.sub.5 alkyl within the C.sub.1 -C.sub.5 alkylthio, C.sub.1 -C.sub.5
 alkylsulfinyl or C.sub.1 -C.sub.5 alkylsulfonyl group.
 If the compounds of general formula I (B=--CH.sub.2) are present as salts,
 this can be in the form of, for example, hydrochloride, sulfate, nitrate,
 tartrate or benzoate.
 If the compounds according to the invention are present as racemic
 mixtures, they can be separated into pure, optically active forms
 according to the methods of racemate separation that are familiar to one
 skilled in the art. For example, the racemic mixtures can be separated by
 chromatography into pure isomers on an even optically active carrier
 material (CHIRALPAK AD.RTM.). It is also possible to esterify the free
 hydroxy group in a racemic compound of general formula I with an optically
 active acid and to separate the diastereoisomeric esters that are obtained
 by fractionated crystallization or by chromatography, and to saponify the
 separate esters in each case into the optically pure isomers. For example,
 mandelic acid, camphorsulfonic acid or tartaric acid can be used as
 optically active acid.
 Preferred according to this invention are those compounds of general
 formula I, in which:
 R.sup.1 and R.sup.2 are the same or different and stand for a hydrogen
 atom, a methyl or ethyl group, and also together with the C-atom of the
 chain stand for a cyclopropyl ring, and/or
 R.sup.3 stands for a C.sub.1 -C.sub.5 perfluoroalkyl group, and/or
 A stands for a benzene, naphthalene or thiophene ring that is optionally
 substituted by one or more radicals, selected from fluorine atoms,
 chlorine atoms, bromine atoms, methyl groups, ethyl groups,
 (CH.sub.2).sub.n group (n=3,4,5), which with 2 adjacent C atoms of
 aromatic compound A forms a ring with n+2 links and can contain
 unsaturations; vinyl groups, hydroxy groups, methoxy groups, ethoxy
 groups, and/or either
 X.sup.3a stands for a hydrogen atom or a C.sub.1 -C.sub.5 alkyl group, or
 X.sup.3a and X.sup.3b are the same or different and stand for a hydrogen
 atom or a C.sub.1 -C.sub.5 alkyl group and/or
 X.sup.4, X.sup.6 and X.sup.7 are the same or different, and stand for,
 independently of one another, a hydrogen atom or a halogen atom, and/or
 Y' stands for a C.sub.1 -C.sub.5 alkyl group or a C.sub.1 -C.sub.5
 perfluoroalkyl group, and/or
 Y.sup.6, Y.sup.7 and Y.sup.8 are the same or different and, independently
 of one another, stand for a hydrogen atom or a halogen atom,
 and the other substituents all have the meanings that are indicated in
 Formula 1.
 In addition, those compounds of general formula I in which Ar stands for a
 ring system of partial formula 6, 7, 10 or 11 are preferred.
 The compounds that are mentioned below are especially preferred according
 to the invention:
 4-Bromo-5-(2-hydroxy-4-methyl-4-phenyl-2-trifluoromethyl-valeroylamino)-pht
 halide,
 6-bromo-5-(2-hydroxy-4-methyl-4-phenyl-2-trifluoromethyl-valeroylamino)-pht
 halide,
 5-(2-hydroxy-4-methyl-2-pentafluoroethyl-4-phenyl-valeroylamino)-phthalide,
 5-[2-hydroxy-4-(3-methoxyphenyl)-4-methyl-2-trifluoromethyl-valeroylamino]-
 phthalide,
 5-[2-(hydroxy-4-(4-methoxyphenyl)-4-methyl-2-trifluoromethyl-valeroylamino]
 -phthalide,
 5-[2-hydroxy-4-(2-hydroxyphenyl)-4-methyl-2-trifluoromethyl-valeroylamino]-
 phthalide,
 5-[4-(2-fluorophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeroylamino]-p
 hthalide,
 5-[4-(4-fluorophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeroylamino]-p
 hthalide,
 5-[4-(4-chlorophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeroylamino]-p
 hthalide,
 5-[4-(4-bromophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeroylamino]-ph
 thalide,
 5-[2-hydroxy-4-methyl-4-(4-tolyl)-2-trifluoromethyl-valeroylamino]-phthalid
 e,
 5-[2-hydroxy-4-methyl-4-(3-tolyl)-2-trifluoromethyl-valeroylamino]-phthalid
 e,
 5-[4-(4-cyanophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeroylamino]-ph
 thalide,
 5-[4-(3,4-dimethylphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeroylamin
 o]-phthalide,
 5-[4-(3,5-dimethylphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeroylamin
 o]-phthalide,
 5-[2-hydroxy-4-(2-methoxy-5-methylphenyl)-4-methyl-2-trifluoromethyl-valero
 ylamino]-phthalide,
 5-[4-(5-chloro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valero
 ylamino]-phthalide,
 5-[4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valero
 ylamino]-phthalide,
 5-[2-hydroxy-4-(2-hydroxy-5-methylphenyl)-4-methyl-2-trifluoromethyl-valero
 ylamino]-phthalide,
 5-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valero
 ylamino]-phthalide,
 5-[4-(2-fluoro-4-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valero
 ylamino]-phthalide,
 5-[4-(3-fluoro-4-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valero
 ylamino]-phthalide,
 5-(2-hydroxy-4-phenyl-2-trifluoromethyl-valeroylamino)-phthalide,
 5-[2-hydroxy-4-(2-methoxyphenyl)-4-methyl-2-trifluoromethyl-valeroylamino]-
 phthalide,
 5-[4-(5-chloro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valero
 ylamino]-phthalide,
 5-(2-hydroxy-4-phenyl-2-trifluoromethyl-pentylamino)-phthalide,
 5-(2-hydroxy-4-methyl-4-phenyl-2-trifluoromethyl-pentylamino)-phthalide,
 5-[4-(4-fluorophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentylamino]-pht
 halide,
 5-[4-(5-fluoro-2-hydroxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentyl
 amino]-phthalide,
 6-acetyl-5-(2-hydroxy-4-methyl-4-phenyl-2-trifluoromethyl-valeroylamino)-ph
 thalide,
 5-[4-(3-fluoro-4-hydroxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valero
 ylamino]-phthalide,
 5-[4-(3-fluorophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeroylamino]-p
 hthalide,
 6-(3-hydroxy-3-methyl-1-butinyl)-5-(2-hydroxy-4-methyl-4-phenyl-2-trifluoro
 methyl-valeroylamino)-phthalide,
 6-[2-hydroxy-4-methyl-4-phenyl-2-trifluoromethyl-valeroylamino)-4-methyl-2,
 3-benzoxazin-1-one,
 6-(2-hydroxy-4-methyl-4-phenyl-2-trifluoromethyl-valeroylamino)-4-trifluoro
 methyl-2,3-benzoxazin-1-one,
 4-ethyl-6-(2-hydroxy-4-phenyl-2-trifluoromethyl-pentylamino)-2,3-benzoxazin
 -1-one,
 4-ethyl-6-[2-hydroxy-4-(2-methoxyphenyl)-4-methyl-2-trifluoromethyl-valeroy
 lamino]-2,3-benzoxazin-1-one,
 6-[2-hydroxy-4-(2-methoxyphenyl)-4-methyl-2-trifluoromethyl-valeroylamino]-
 4-methyl-2,3-benzoxazin-1-one,
 4-ethyl-6-[2-hydroxy-4-methyl-4-(4-methylphenyl)-2-trifluoromethyl-valeroyl
 amino]-2,3-benzoxazin-1-one,
 6-[4-(4-bromophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeroylamino]-4-
 ethyl-2,3-benzoxazin-1-one,
 4-ethyl-6-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethy
 l-valeroylamino]-2,3-benzoxazin-1-one,
 6-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valero
 ylamino]-4-methyl-2,3-benzoxazin-1-one,
 1-(4-nitro-3-trifluoromethylanilino)-4-phenyl-2-trifluoromethyl-2-pentanol,
 1-(4-nitro-3-trifluoromethylanilino)-4-phenyl-2-trifluoromethyl-2-pentanol,
 5-(2-hydroxy-4,4-dimethyl-2-trifluoromethyl-5-hexenoylamino)-phthalide,
 5-[2-hydroxy-3-(1-phenyl-cyclopropyl)-2-trifluoromethyl-propionylamino]-pht
 halide,
 5-[2-hydroxy-3-(1-phenyl-cyclobutyl)-2-trifluoromethyl-propionylamino]-phth
 alide,
 5-[2-hydroxy-3-(1-phenyl-cyclohexyl)-2-trifluoromethyl-propionylamino]-phth
 alide,
 2-hydroxy-4-methyl-2-trifluoromethyl-4-(4-vinylphenyl)-valeric acid,
 4-(4-acetylphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric acid,
 4-(4-acetyl-3-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric
 acid,
 4-(4-cyanophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric acid,
 4-(4-carbamoylphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric acid,
 4-(4-cyano-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric
 acid,
 4-(3-bromo-4-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric
 acid,
 2-Hydroxy-4-methyl-4-(3-nitro-4-methoxyphenyl)-2-trifluoromethyl-valeric
 acid,
 4-(4-iodo-2-methoxyphenyl)-4-methyl-2-oxo-valeric acid,
 4-(3-chlorophenyl)-4-methyl-2-oxo-valeric acid,
 4-(3-bromophenyl)-4-methyl-2-oxo-valeric acid,
 4-(2-iodophenyl)-4-methyl-2-oxo-valeric acid,
 4-(3-iodophenyl)-4-methyl-2-oxo-valeric acid,
 4-(4-iodophenyl)-4-methyl-2-oxo-valeric acid,
 4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxo-valeric acid,
 4-(4-bromo-2-methoxyphenyl)-2-oxo-valeric acid,
 3-(1-phenylcyclopentyl)-pyruvic acid,
 6-[3-(1-phenyl-cyclopropyl)-2-oxo-propionylamino]-4-methyl-2,3-benzoxazin-1
 -one,
 6-[3-(1-phenyl-cyclobutyl)-2-oxo-propionylamino]-4-methyl-2,3-benzoxazin-1-
 one,
 6-[3-(1-phenyl-cyclohexyl)-2-oxo-propionylamino]-4-methyl-2,3-benzoxazin-1-
 one,
 5-[4-(4-iodo-2-methoxyphenyl)-4-methyl-2-oxo-valeroylamino)-phthalide,
 5-[4-(4-iodophenyl)-4-methyl-2-oxo-valeroylamino)-phthalide,
 5-[4-(3-iodophenyl)-4-methyl-2-oxo-valeroylamino)-phthalide,
 5-[4-(4-bromo-2-methoxyphenyl)-2-oxo-valeroylamino)-phthalide,
 5-[3-(1-phenyl-cyclopentyl)-2-oxo-propionylamino]-phthalide,
 6-[4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxo-valeroylamino)-4-methyl-2,3-
 benzoxazin-1-one,
 6-[4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxo-valeroylamino)-4-ethyl-2,3-b
 enzoxazin-1-one,
 6-(2-hydroxy-2,4-dimethyl-4-phenyl-valeroylamino)-4-methyl-2,3-benzoxazin-1
 -one,
 5-[4-(3-chloro-4-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valero
 ylamino)-phthalide,
 5-[4-(3-chloro-4-hydroxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valero
 ylamino]-phthalide.
 All above-mentioned compounds are especially preferred in the form of the
 optical antipodes or the separate diastereomers.
 In the gestagen receptor bonding test on the gestagenic action using
 cytosol from rabbit uterus homogenate and from .sup.3 H-progesterone as a
 reference substance, the new compounds show a strong to very strong
 affinity to the gestagen receptor (see Table 1).
 TABLE 1

Competition

Factor
 (Reference
 Substance
 Example No. Structure .sup.3
 H-Progesterone)
 (*) (Melting point 141-142.degree. C.) ##STR6##
 17
 (*) (Melting point 161.degree. C.) ##STR7##
 2.0
 65 ##STR8##
 0.17
 104 ##STR9## 0.1
 106 ##STR10##
 0.55
 (*) EP 0 253 500 B1, Example 1
 In addition to their gestagenic action, which is pronounced to different
 degrees depending on the compound of general formula I that is considered,
 the new compounds also are distinguished by a more or less strongly
 pronounced affinity to the androgen receptor. The androgen receptor
 bonding test on androgenic action was carried out using cytosol that
 consists of rat prostate homogenate and .sup.3 H-methyltrienolone as a
 reference substance.
 The new compounds are thus represented relative to the gestagenic compounds
 from EP 0 253 500 B1 as compounds with a quite novel mix profile, which
 consists of gestagenic and androgenic action.
 For the compounds of general formula I according to the invention, in this
 case all three of the cases that are possible below are found, which based
 on the competition factors on progesterone receptor (KF.sub.Prog) and
 androgen receptor (KF.sub.Andro) are classified within the scope of this
 invention as follows:
 1) Compounds with stronger gestagenic action and less pronounced androgenic
 action (KF.sub.Prog &lt;1 and KF.sub.Andro &gt;5);
 2) Compounds with stronger androgenic action and less pronounced gestagenic
 action (KF.sub.Andro &lt;5 and KF.sub.Prog &gt;1);
 3) Compounds with pronounced gestagenic and pronounced androgenic action
 (KF.sub.Prog &lt;1 and KF.sub.Andro &lt;5).
 Depending on their classification according to 1), 2) or 3), the new
 compounds according to the invention can be used for different medical or
 pharmaceutical purposes.
 In the case of the compounds that are classified under 1) with stronger
 gestagenic action and less pronounced androgenic action, these are very
 effective gestagens, which, like the already numerous known gestagenic
 compounds, are suitable for preserving pregnancies in the case of
 parenteral administration and in the case of oral administration.
 In combination with an estrogen, combination preparations are obtained that
 can be used for contraception and for the treatment of menopausal
 symptoms.
 Based on their high gestagenic action, the new compounds of general formula
 I that are classified under 1) can be used, for example, alone or in
 combination with estrogens in contraceptive preparations. However, all
 other applications that are known for gestagen are now open to these new
 compounds (see, e.g., "Kontrazeption mit Hormonen [Contraception with
 Hormones]," Hans-Dieter Taubert and Herbet Kuhl, Georg Thieme Verlag
 Stuttgart - New York, 1995).
 Suitable dosages can be determined as a matter of routine, e.g., by
 determining the bioequivalency, for example in the pregnancy-maintenance
 test, relative to a known gestagen for a specific use, for example an
 amount that is bioequivalent to 30 to 150 .mu.g of levonorgestrel for
 contraception.
 The dosage of the compounds according to the invention under 1) in
 contraceptive preparations is preferably to be 0.01 to 2 mg per day.
 The gestagenic and estrogenic active ingredient components are preferably
 administered orally together in contraceptive preparations. The daily dose
 is preferably administered once.
 As estrogens, all natural and synthetic compounds that are known as
 estrogenically active are suitable.
 As natural estrogens, these are especially estradiol and also its
 longer-acting esters, such as valerate, etc. or estriol.
 Preferably, however, synthetic estrogens such as ethinyl-estradiol,
 14.alpha.,17.alpha.-ethano-1,3,5(10)-estratriene-3-17.beta.-diol (WO
 88/01275),
 14.alpha.,17.alpha.-ethano-1,3,5(10)-estratriene-3,16.alpha.,17.beta.-trio
 l (WO 91/08219) or the 15,15-diallyl derivatives of the estradiol, and of
 these especially 15,16-dimethylestradiol (WO 95/04070) can be mentioned.
 As a synthetic estrogen, ethinylestradiol is preferred.
 Also, the estratrien-3-aminosulfonates that have become known recently (WO
 96/05216 and WO 96/05217), derived from estradiol or ethinylestradiol,
 which are distinguished by low hepatic estrogeneity, are suitable as
 estrogens for common use with the compounds of general formula I that are
 classified under 1). Finally, the 14.alpha.,15.alpha.-methylene steroids
 from the estrane series, especially the
 14.alpha.,15.alpha.-methylene-17.alpha.-estradiol as well as the
 corresponding 3-aminosulfonate derivatives can be mentioned.
 The estrogen is administered in an amount that corresponds to that of 0.01
 to 0.05 mg of ethinylestradiol.
 The new compounds of general formula I that are classified under 1) can
 also be used in preparations for treatment of gynecological disorders and
 for substitution therapy. Because of their advantageous profile of action,
 these compounds according to the invention are especially well suited for
 treatment of premenstrual symptoms, such as headaches, depression, water
 retention and mastodynia. The daily dose in the treatment of premenstrual
 symptoms is approximately 1 to 20 mg.
 Analogously to what is already known for other gestagens, the new compounds
 can also be used for treating endometrioses.
 Finally, these new compounds can also be used as gestagenic components in
 the compositions for female birth control that have recently become known
 and that are distinguished by the additional use of a competitive
 progesterone antagonist (H. B. Croxatto and A. M. Salvatierra in Female
 Contraception and Male Fertility Regulation, ed. by Runnebaum, Rabe &
 Kiesel--Vol. 2, Advances in Gynecological and Obstetric Research Series,
 Parthenon Publishing Group--1991, page 245; WO 93/17686, WO 93/21927, U.S.
 Pat. No. 5,521,166).
 The dosage lies in the range that is already indicated, and the formulation
 can be carried out as in conventional OC-preparations. The administration
 of the additional, competitive progesterone antagonist can in this case
 also be performed sequentially.
 Those compounds of the general formula, which are to be categorized as
 above under 2) and 3), i.e., compounds that have a strong androgenic
 action (androgenic gestagens), can be used for the production of
 pharmaceutical preparations for male birth control.
 Currently, in several WHO studies, the contraceptive action of a
 combination that consists of an orally administered gestagen
 (Depot-medroxy progesterone acetate, levonorgestrel ester, cyproterone
 acetate) is tested on men with a parenterally administered androgen
 (testosterone oenanthate).
 By contrast, birth control in men is possible with these compounds in one
 dosage form, specifically an oral dosage form or a dosage form that is to
 be administered transdermally.
 In addition, the compounds according to the invention with androgenic
 action can be used with older males for male HRT (Hormone Replacement
 Therapy).
 Those compounds of general formula I, which can more likely be classified
 under 2), i.e., compounds with mainly androgenic action and weaker
 gestagenic action, can be used for male hormone therapy. Preparations for
 treating a hyper-gonadism and for treating male infertility and
 disturbances of potency can be produced with them.
 For male birth control and for treating the above-mentioned androgenic
 disease agents, the compounds according to the invention are used in the
 dosages that are equivalent in action to the testosterone oenanthate
 amounts that are used in the WHO studies or to the dosage that is already
 in androgen therapy of compounds used.
 Amounts that are equivalent in action are those amounts that, in the test
 on androgenic action on the seminal vesicles and/or prostate of the rat
 (Hershberger Test) achieve comparable action.
 For HRT in man, to date a substitution dose of approximately 10 mg/day of
 testosterone oenanthate is used.
 For male birth control studies that are performed by the WHO, different
 testosterone esters (oenanthate, bucyclate, undecanoate) are used in the
 range of approximately 10-30 mg/day.
 At this point it should be pointed out that the transitions between 1), 2)
 and 3), as regards the correlation according to the invention of various
 indications with these varying mix profiles 1), 2) and 3), are smooth. The
 compounds that more likely lie on the edge of the indicated KF areas based
 on their KF.sub.Prog and/or KF.sub.Andro, can easily be used also for the
 indications that are assigned to the adjacent mix profile.
 The compounds of general formula I also partially show actions on the
 glucocorticoid and/or mineral corticoid receptor.
 The formulation of the pharmaceutical preparations based on the new
 compounds is carried out in a way that is known in the art, by the active
 ingredient, optionally in combination with an estrogen, being processed
 with the vehicles that are commonly used in galenicals, diluents,
 optionally taste correctives, etc., and conveyed in the desired form of
 administration.
 For the preferred oral administration, especially tablets, coated tablets,
 pills, suspension or solutions are suitable.
 For parenteral administration, especially oily solutions, such as, for
 example, solutions in sesame oil, castor oil and cottonseed oil, are
 suitable. To increase solubility, solubilizers, such as, for example,
 benzyl benzoate or benzyl alcohol, can be added.
 The compounds of general formula I can also be administered continuously by
 an intrauterine release system (intrauterine system=IUS; e.g.,
 MIRENA.RTM.); the release rate of the active compound(s), is selected in
 this case in such a way that the dose that is released daily lies within
 the already indicated dosage range. It is also possible to incorporate the
 substances according to the invention in a transdermal system and thus to
 administer them transdermally.
 The compounds of general formula I according to the invention can be
 produced as described below.
 Production Process
 1. A carbonyl compound of general formula II
 ##STR11##
 in which A, B, Ar, R.sup.1 and R.sup.2 have the meaning that is indicated
 in formula I, is reacted with a compound of general formula C.sub.n
 F.sub.2n+1 --SiR.sup.3, in which R.sup.3 has the meaning that is indicated
 in general formula 1, in the presence of a catalyst or with an alkyl metal
 compound, for example a Grignard reagent or a lithium alkyl, to a compound
 of formula I. As catalysts, fluoride salts or basic compounds such as
 alkali carbonates are suitable (J. Amer. Chem. Soc. 111, 393 (1989)).
 2. A compound of general formula III
 ##STR12##
 in which A, B, R.sup.1, R.sup.2 and R.sup.3 have the meaning that is
 indicated in formula 1 and FG means a leaving group, is reacted with a
 compound Ar--NH--R.sup.11, whereby R.sup.11 means a hydrogen atom or a
 C.sub.1 -C.sub.5 acyl group, and Ar has the meaning that is indicated in
 general formula I, whereby optionally then radical R.sup.11 is cleaved off
 to obtain a compound of formula I. In this case, the compound of general
 formula III optionally can be formed only as an intermediate product,
 e.g., this can be an acid chloride that is formed as an intermediate
 product from a corresponding carboxylic acid. As leaving groups
 3. A compound of general formula IV
 ##STR13##
 in which A, R.sup.1, R.sup.2 and R.sup.3 have the meaning that is indicated
 in formula I, is reacted with a compound of formula Ar--NH--R.sup.11,
 whereby R.sup.11 and Ar have the above-indicated meanings, whereby
 optionally then radical R.sup.11 is cleaved off, to obtain a compound of
 formula I with B in the meaning of a CH.sub.2 group.
 4. A compound of formula I, which in radical A or in radical Ar contains
 the grouping aryl-X, whereby "aryl" means an isocyclic or heterocyclic
 aromatic compound that corresponds to the definitions that are given for
 formula I and X means a bromine or iodine atom or the group --O--SO.sub.2
 R.sup.12, in which R.sup.12 means a C.sub.1 -C.sub.5 perfluoroalkyl group,
 is reacted under metal catalysis to compound aryl-R.sup.13 according to
 processes that are known in the art with a compound of formula R.sup.13
 -Y, whereby R.sup.13 represents an optionally substituted aryl, ethenyl or
 ethinyl radical and Y represents a hydrogen atom (J. Org. Chem. 43, 2947
 (1978)), group B (O--R.sup.14).sub.2 (J. Org. Chem. 58, 2201 (1993)) or
 Sn(R.sup.15).sub.3 (J. Org. Chem. 52, 422 (1987)) with R.sup.14 and
 R.sup.15 meaning a phenyl radical or C.sub.1 -C.sub.5 alkyl and R.sup.14
 also represents hydrogen, Mg-halogen or an alkali metal atom.
 5. In a compound of formula I, which contains an alkoxy or acyloxy
 substituent in A or Ar, the OH group is released, and optionally
 etherified or esterified in another reaction or, after conversion into a
 1-phenyl-5-tetrazolylether, is completely eliminated by hydrogenation (J.
 Amer. Chem. Soc. 88, 4271 (1966)).
 Of all the foregoing process variants, 1. and 2. are suitable for the
 production of all compounds that fall under general formula I.
 Compounds of general formula I can be produced with the third variant, in
 which B stands for a --CH.sub.2 group.
 Using the fourth and fifth process variants, functionalizations of already
 existing compounds of general formula I can be undertaken.
 Compounds that were produced according to one of the processes above and in
 which A is an optionally substituted aromatic ring, optionally can be
 selectively substituted at this aromatic radical according to known
 processes. Examples of this process are the catalytic hydrogenation of
 multiple bonds, nitration and halogenation.
 The starting materials that are used in the examples are produced as
 follows:
 Production of Starting Materials
 4-Methyl-4-phenyl-2-oxovaleric acid
 A Grignard solution that is produced from 26.4 g of magnesium and 162 ml of
 2-methyl-2-phenyl-1-chloropropane in 150 ml of diethyl ether was added in
 drops to 600 ml of oxalic acid diethyl ester at -30.degree. C. After 2
 hours at room temperature, it was added to ammonium chloride solution,
 extracted with diethyl ether, dried (Na.sub.2 SO.sub.4) and distilled in
 fractionated form; 84 g of ethyl ester (boiling point 115-120.degree.
 C./0.03 hPa), which is dissolved in 1 l of methanol, is obtained, mixed
 with 500 ml of 1m sodium hydroxide and stirred for 1.5 hours at room
 temperature. After the methanol is evaporated in a vacuum, the residue is
 dispersed between water and diethyl ether, the aqueous phase is acidified
 with hydrochloric acid and extracted with diethyl ether. After
 concentration by evaporation, 57 g of 4-methyl-4-phenyl-2-oxovaleric acid
 is obtained as a thick oil.
 4,4-Dimethyl-2-oxo-5-hexenoic acid
 36 g of 3,3-dimethyl-4-pentenoic acid is obtained as an oil from 50 g of
 3,3-dimethyl-4-pentenoic acid methyl ester by saponification with 10%
 potassium hydroxide. By stirring with thionyl chloride (20 hours, room
 temperature), the acid chloride is obtained, boiling point 59.degree.
 C./30 hPa. 16 g of it is stirred with 15 g of trimethylsilylcyanide and
 0.16 g of zinc iodide for 4 days. After distillation, 13 g of
 4,4-dimethyl-2-oxo-5-hexenoic acid nitrile, boiling point 75-85.degree.
 C./30 hPa, is obtained. 2 g of it is saturated with 0.6 ml of methanol in
 13 ml of hexane while being cooled with ice with hydrochloric-acid gas,
 and it is mixed for 2 hours with water. From the hexane phase, after
 drying (Na.sub.2 SO.sub.4) and concentration by evaporation, 0.558 g of
 4,4-dimethyl-2-oxo-5-hexenoic acid methyl ester, boiling point 48.degree.
 C./0.003 hPa, is obtained. 0.535 g of it is saponified with 1.3 ml of 3N
 sodium hydroxide solution, whereby 0.32 g of 4,4-dimethyl-2-oxo-5-hexenoic
 acid is obtained as a yellowish liquid.
 3-(1-Phenyl-cyclobutyl)-2-oxo-propionic acid
 10 g of 1-phenyl-cyclobutanecarbonitrile, dissolved in 70 ml of toluene, is
 mixed with 56 ml of diisobutylaluminum hydride in toluene (1.2 molar) at
 -72 to -69.degree. C. After 4 hours at -75.degree. C., 30 ml of ethyl
 acetate is added in drops. After heating to room temperature, additional
 ethyl acetate and water are added. It is filtered on diatomaceous earth,
 the organic phase is separated, dried (Na.sub.2 SO.sub.4) and concentrated
 by evaporation. After chromatography on silica gel (hexane with 0-10%
 ethyl acetate), 7.6 g of 1-phenyl-cyclobutanecarbaldehyde is obtained. 3 g
 of it is dissolved in 10 ml of tetrahydrofuran and added in drops at
 0.degree. C. to a solution, in which previously 5 g of
 triethyl-2-ethoxyphosphonoacetate in 70 ml of tetrahydrofuran was mixed at
 0.degree. C. with 10.3 ml of a 2 molar solution of lithium
 diisopropylamide in tetrahydrofuran/heptane/ethylbenzene. After 20 hours
 at room temperature, water is added, it is extracted with ethyl acetate,
 dried (Na.sub.2 SO.sub.4) and concentrated by evaporation. 2 g of this
 crude product is saponified with 28 ml of 1N sodium hydroxide solution.
 1.32 g of the acid, which is heated for 20 hours to 90.degree. C. with 25
 ml of 1 molar sulfuric acid while being stirred vigorously, is obtained.
 After extraction with ether, drying (Na.sub.2 SO.sub.4) and concentration
 by evaporation, 0.89 g of 3-(1-phenyl-cyclobutyl)-2-oxopropionic acid is
 obtained as a yellowish oil.
 3-[1-(2-Methoxyphenyl)-cyclopropyl]-2-oxo-propionic acid
 Corresponding to J. Org. Chem. 40 (1975) 3497, 16.7 g of
 2-methoxyphenylacetonitrile, 158 ml of lithium triisopropyl-amide (2 mol
 solution) and 46.7 ml of 1,2-dichloroethane in 96 ml of tetrahydrofuran
 and 58.6 ml of hexamethylphosphoric acid triamide are reacted with one
 another. 5.6 g of 1-(2-methoxy-phenyl)-cyclopropyl-carbonitrile, boiling
 point 104-115.degree. C./0.1 mbar, which was also reacted as described for
 3-(1-phenyl-cyclobutyl)-2-oxo-propionic acid, is obtained.
 3-[1-(2-Methoxyphenyl)-cyclopropyl]-2-oxo-propionic acid is thus obtained
 as an oil.
 Analogously to the process that is described for
 3-(1-phenyl-cyclobutyl)-2-oxo-propionic acid and for
 3-[1-(2-methoxyphenyl)-cyclopropyl]-2-oxo-propionic acid, the acids that
 are described in Table 2 were obtained.
 TABLE 2
 ##STR14##
 Z.sup.n Melting Point
 Example n (.noteq. H) (.degree. C.)
 1 3-F oil
 1 2-Cl 60-63
 1 4-Cl oil
 1 2-Br 49-54
 1 3-Br oil
 1 2,4-Cl.sub.2 185-190
 1 3-OCH.sub.3 oil
 1 3-CF.sub.3 oil
 3 oil
 3 4-CH.sub.3 50-61
 4 4-OCH.sub.3 oil
 3-(1-Phenyl-cyclopropyl)-2-oxo-propionic acid
 is obtained analogously to the process that is described for
 3-(1-phenyl-cyclobutyl)-2-oxo-propionic acid.
 3-(1-Phenyl-cyclohexyl)-2-oxo-propionic acid
 is obtained analogously to the process that is described for
 3-(1-phenyl-cyclobutyl)-2-oxo-propionic acid.
 4-(3-Methoxyphenyl)-4-methyl-2-oxo-valeric acid 4.2 ml of a 0.6 m solution
 of 3-methoxyphenylmagnesium bromide in tetrahydrofuran is mixed at
 -70.degree. C. with 257 mg of copper bromide-dimethylsulfide complex and
 then stirred at -40.degree. C. for 20 minutes. It is cooled again to
 -70.degree. C., and 0.33 ml of 1,3-dimethyl-tetrahydro-2-1H-pyrimidinone
 and a mixture of 400 mg of 4-methyl-2-oxo-3-pentenoic acid methyl ester
 (Liebigs Annalen [Liebigs Annals] 1974, 477) and 0.71 ml of
 trimethylchlorosilane in 3.5 ml of tetrahydrofuran are slowly added. It is
 stirred for one hour at -70.degree. C. and then heated to room
 temperature. Then, 2N hydrochloric acid and ethyl acetate are added, the
 ethyl acetate phase is separated, it is concentrated by evaporation, and
 the residue is dissolved in 5 ml of dichloromethane. After 200 mg of
 tetrabutylammonium fluoride is added, it is left at room temperature for
 one hour, then washed with water, and the dichloromethane phase is dried
 (Na.sub.2 SO.sub.4) and concentrated by evaporation. After chromatography
 on silica gel with hexane/ethyl acetate (97:3), 63 mg of
 4-(3-methoxyphenyl)-4-methyl-2-oxo-valeric acid-methyl ester, which is
 mixed with 1 ml of potassium hydroxide in methanol (10%), is obtained.
 After 45 minutes, it is concentrated by evaporation, the residue is
 dissolved in water and extracted with diethyl ether. The aqueous phase is
 then acidified with 6N hydrochloric acid and extracted with diethyl ether.
 The diethyl ether phase is dried (Na.sub.2 SO.sub.4) and concentrated by
 evaporation. 50 mg of 4-(3-methoxyphenyl)-4-methyl-2-oxo-valeric acid is
 obtained.
 2-Hydroxy-4-methyl-4-phenyl-2-trifluoromethyl-valeric acid
 The Grignard reagent is produced from 1.5 g of magnesium and 10 g of
 2-methyl-2-phenylpropyl chloride in 100 ml of diethyl ether, which yields
 9.5 g of 2-hydroxy-4-methyl-4-phenyl-2-trifluoromethyl-valeric acid ethyl
 ester, boiling point 90.degree. C./0.045 hPa, after reaction with 10 g of
 trifluoro-pyruvic acid ethyl ester.
 7.5 g of the ethyl ester is refluxed with 100 ml of potassium hydroxide in
 methanol (10%) for 18 hours. After concentration by evaporation in a
 vacuum, the residue is dissolved in water and extracted with diethyl
 ether. The aqueous phase is acidified with 2N hydrochloric acid and
 extracted with diethyl ether. After the solvent is concentrated by
 evaporation, 3.2 g of
 2-hydroxy-4-methyl-4-phenyl-2-trifluoromethyl-valeric acid is obtained as
 colorless crystals, boiling point 124-126.degree. C.
 4-(5-Fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric
 acid
 1.3 g of anhydrous zinc chloride and 13.2 g of granular manganese are
 heated to boiling in 100 ml of tetrahydrofuran and boiled with 0.2 ml of
 methallyl bromide for 30 minutes. Then, the solution of 25 g of methallyl
 bromide and 17 g of trifluoropyruvic acid ethyl ester in 80 ml of
 tetrahydrofuran is added in drops at boiling heat over 2 hours, and boiled
 for another hour. Then, while being cooled with ice, saturated ammonium
 chloride solution and 300 ml of ethyl acetate are added, stirred for 30
 minutes at 0.degree. C., and the separated ethyl acetate phase is washed
 with saturated ammonium chloride solution and three times with water. The
 solvent is dried (Na.sub.2 SO.sub.4) and concentrated by evaporation, and
 the residue is distilled in a vacuum. 17.6 g of
 2-hydroxy-4-methylene-2-trifluoromethyl-valeric acid ethyl ester, boiling
 point 48.degree. C./1 hPa, is obtained.
 0.8 g of anhydrous aluminum chloride is added to 5 ml of 4-fluoranisole and
 0.9 g of 2-hydroxy-4-methylene-2-trifluoromethyl-valeric acid ethyl ester.
 After 40 hours of stirring at room temperature, it is added to ice-cooled
 2N hydrochloric acid and extracted with ethyl acetate. The ethyl acetate
 phase is washed with 1N hydrochloric acid and water, dried (Na.sub.2
 SO.sub.4) and concentrated by evaporation. After chromatography on silica
 gel with hexane/ethyl acetate (1:1), 1 g of
 4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric
 acid ethyl ester, melting point 38-39.degree. C., is obtained.
 1.9 g of
 4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric
 acid ethyl ester is refluxed with 40 ml of potassium hydroxide in methanol
 (10%) for 2 hours. After the solvent is concentrated by evaporation in a
 vacuum, water is added, it is extracted with hexane, and the separated
 water phase is acidified with 6N hydrochloric acid. After extraction with
 ethyl acetate, the ethyl acetate phase is washed with water, dried
 (Na.sub.2 SO.sub.4) and concentrated by evaporation. The residue is
 crystallized from hexane. 1.55 g of
 4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric
 acid, melting point 102-104.degree. C., is obtained.
 2-Hydroxy-4-methyl-4-(2-thienyl)-2-trifluoromethyl-valeric acid and
 2-hydroxy-4-methyl-4-(3-thienyl)-2-trifluoromethyl-valeric acid
 The mixture of 2-hydroxy-4-methyl-4-(2-thienyl)-2-trifluoromethyl-valeric
 acid and 2-hydroxy-4-methyl-4-(3-thienyl)-2-trifluoromethyl-valeric acid
 (9:1), melting point 150-151.degree. C., was produced analogously
 The acids of Table 3 were produced analogously.
 TABLE 3
 ##STR15##
 Z.sup.n Melting Point
 (.noteq. H) (.degree. C.)
 Z.sup.4 = CH.sub.3 136-138
 Z.sup.3 = Z.sup.4 = CH.sub.3 115-117
 Z.sup.3 = Z.sup.5 = CH.sub.3 118
 Z.sup.4 = Br 131-132
 Z.sup.4 = Cl 133-135
 Z.sup.4 = F 140-141
 Z.sup.2 = OCH.sub.3 98-99
 Z.sup.4 = OCH.sub.3 129-130
 Z.sup.2 = Z.sup.5 = OCH.sub.3 136-137
 Z.sup.2 = OCH.sub.3, Z.sup.5 = CH.sub.3 106-107
 Z.sup.2 = OCH.sub.3, Z.sup.4 = F 103-106
 Z.sup.2 = OCH.sub.3, Z.sup.5 = F 102-104
 Z.sup.4 = OCH.sub.3, Z.sup.2 = F 122-124
 Z.sup.4 = OCH.sub.3, Z.sup.3 = F 108-109
 Z.sup.2 = OCH.sub.3, Z.sup.5 = Cl 103-105
 Z.sup.3 /Z.sup.4 = (CH.sub.2).sub.3 118-119
 Z.sup.3 /Z.sup.4 = --CH.dbd.CH--CH.dbd.CH-- 137
 Z.sup.2 = OCH.sub.3, Z.sup.4 = Br 115-116
 Z.sup.2 = Br, Z.sup.4 = OCH.sub.3 122-124
 Z.sup.4 = C.sub.6 H.sub.5 162-163
 Z.sup.2 = OCH.sub.3, Z.sup.4 = CH(CH.sub.3).sub.2 137-138
 By conversion according to the standard process, additional acids are
 obtained from the acids above or their precursors:
 2-Hydroxy-4-methyl-2-trifluoromethyl-4-(4-vinylphenyl)-valeric acid
 By heating 4-(4-bromophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric
 acid ethyl ester, tributylvinyltin, tri-o-tolylphosphine and
 bis-tri-o-tolylphosphine-palladium(II) chloride in dimethylformamide to
 120.degree. C.,
 2-hydroxy-4-methyl-2-trifluoromethyl-4-(4-vinylphenyl)-valeric acid ethyl
 ester, which provides the title compound, melting point 73-74.degree. C.,
 by alkaline saponification, is obtained.
 4-(4-Acetylphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric acid
 Analogously to the compound above of
 4-(4-bromophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric acid ethyl
 ester, tributyl-1-ethoxyvinyltin, tri-o-tolylphosphine and
 bis-tri-o-tolylphosphine-palladium(II) chloride in dimethylformamide to
 120.degree. C. and subsequent acidic hydrolysis of the enol ether and
 alkaline saponification, melting point 158-162.degree. C.
 4-(4-Acetyl-3-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric
 acid
 Analogously to the compound above of
 4-(4-bromo-3-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric
 acid ethyl ester, tributyl-1-ethoxyvinyltin, tri-o-tolylphosphine and
 bis-tri-o-tolylphosphine-palladium(II) chloride in dimethylformamide to
 120.degree. C., oil.
 4-(4-Cyanophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric acid
 From 4-(4-bromophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric acid
 ethyl ester, zinc cyanide and tetrakis-triphenylphosphine-palladium in
 dimethylformamide at 140.degree. C. After saponification, the title acid
 is obtained as a foam.
 4-(4-Carbamoylphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric acid
 is obtained by treating the ethyl ester of the acid above with hydrogen
 peroxide and saponification, melting point 244-245.degree. C.
 4-(4-Cyano-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric
 acid
 From
 4-(4-bromo-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric
 acid ethyl ester, zinc cyanide and tetrakis-triphenylphosphine-palladium
 in dimethylformamide at 140.degree. C. After saponification, the title
 acid is obtained as an amorphous powder.
 4-(3-Bromo-4-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-valeric
 acid
 From 2-hydroxy-4-(4-methoxyphenyl)-4-methyl-2-trifluoromethyl-valeric acid
 ethyl ester by bromation with N-bromosuccinimide in dimethylformamide at
 0.degree. C. and subsequent saponification. Melting point 94-96.degree. C.
 2-Hydroxy-4-methyl-4-(3-nitro-4-methoxyphenyl)-2-trifluoromethyl-valeric
 acid
 This compound is obtained by reaction of 2.5 g of
 2-hydroxy-4-(4-methoxyphenyl)-4-methyl-2-trifluoromethyl-valeric acid
 ethyl ester with 4 ml of 100% nitric acid in 12 ml of trifluoroacetic acid
 for one hour at 0.degree. C., melting point 79-80.degree. C.
 4-(4-Iodo-2-methoxyphenyl)-4-methyl-2-oxo-valeric acid
 3.2 g of 4-iodo-2-methoxybenzoic acid-methyl ester in 10 ml of diethyl
 ether is added to 24.2 mmol of methylmagnesium bromide in 23 ml of diethyl
 ether. After 20 hours, ammonium chloride solution is added, the ether
 phase is separated, dried and concentrated by evaporation. 2.4 g of the
 residue is dissolved in 10 ml of dichloromethane, mixed with 714 mg of
 2-trimethylsilyloxy-acrylic acid-ethyl ester, cooled to -70.degree. C. and
 mixed with 0.27 ml of tin(IV) chloride. After 15 minutes, the solution is
 added to potassium carbonate solution. After extraction with diethyl
 ether, the organic phase is washed with water, dried and concentrated by
 evaporation. 500 mg of the
 4-(4-iodo-2-methoxyphenyl)-4-methyl-2-oxo-valeric acid ethyl ester that is
 thus obtained is stirred with 8.6 ml of 1 M sodium hydroxide in
 ethanol/water (2:1, v/v) for 3 hours at room temperature. After water is
 added, it is extracted with diethyl ether, the aqueous phase is acidified
 with 1 m hydrochloric acid and extracted with diethyl ether. After drying
 and concentration by evaporation, 410 mg of
 4-(4-iodo-2-methoxyphenyl)-4-methyl-2-oxo-valeric acid is obtained as a
 yellowish oil.
 4-(3-Chlorophenyl)-4-methyl-2-oxo-valeric acid
 is obtained analogously to the embodiment above of an amorphous powder.
 4-(3-Bromophenyl)-4-methyl-2-oxo-valeric acid
 is obtained analogously to the embodiment above of an amorphous powder.
 4-(2-Iodophenyl)-4-methyl-2-oxo-valeric acid
 is obtained analogously to the embodiment above as an amorphous powder.
 4-(3-Iodophenyl)-4-methyl-2-oxo-valeric acid
 is obtained analogously to the embodiment above of an amorphous powder.
 4-(4-Iodophenyl)-4-methyl-2-oxo-valeric acid
 is obtained analogously to the embodiment above as an oil.
 4-(5-Fluoro-2-methoxyphenyl)-4-methyl-2-oxo-valeric acid
 is obtained analogously to the embodiment above, melting point
 58-60.degree. C.
 4-(4-Bromo-2-methoxyphenyl)-2-oxo-valeric acid
 is obtained analogously to the embodiment above as an oil.
 3-(1-Phenylcyclopentyl)-pyruvic acid
 is obtained analogously to the embodiment above from 1-phenylcyclopentanol
 with 2-trimethylsilyloxyacrylic acid-ethyl ester and tin(IV) chloride as
 an oil.
 4-Toluenesulfonic acid-(2-hydroxy-4-phenyl-2-trifluoromethyl-pentyl)ester
 A Grignard solution, to which 15 ml of oxalic acid diethyl ester is added
 at -30.degree. C. within 30 minutes, is prepared from 2.6 g of magnesium
 chips and 15 ml of 2-phenyl-1-chloropropane in diethyl ether. It is
 stirred for one hour at -20.degree. C. and for 2 hours at 0.degree. C.,
 and then mixed with saturated ammonium chloride solution. The diethyl
 ether phase is separated, dried (Na.sub.2 SO.sub.4) and concentrated by
 evaporation and distilled in a vacuum. 17.7 g of 2-oxo-4-phenylvaleric
 acid ethyl ester, boiling point 98-100.degree. C./0.03 hPa, is obtained.
 4.4 g of 2-oxo-4-phenylvaleric acid ethyl ester is dissolved in 40 ml of
 tetrahydrofuran and mixed at -78.degree. C. with 3.6 ml of
 trifluoromethyl-trimethylsilane and 2 ml of 1 M tetrabutylammonium
 fluoride in tetrahydrofuran. After 24 hours at -78.degree. C., another 20
 ml of 1 M tetrabutylammonium fluoride in tetrahydrofuran is added. It is
 stirred for 1.5 hours at 0.degree. C., ethyl acetate and saturated common
 salt solution are added, the organic phase is separated, and it is washed
 with saturated common salt solution and water. Then, it is dried (Na.sub.2
 SO.sub.4) and concentrated by evaporation and distilled on a bulb tube.
 4.4 g of 2-hydroxy-4-phenyl-2-trifluoromethyl-valeric acid ethyl ester,
 boiling point 95-100.degree. C./0.04 hPa, is obtained.
 4.35 g of 2-hydroxy-4-phenyl-2-trifluoromethyl-valeric acid ethyl ester is
 dissolved in 100 ml of diethyl ether and stirred at 0.degree. C. with 1.3
 g of lithium aluminum hydride for one hour at 0.degree. C. and for 16
 hours at room temperature. A little water is added while being cooled, and
 it is stirred for one hour. The diethyl ether phase is separated, dried
 (Na.sub.2 SO.sub.4) and concentrated by evaporation and distilled on a
 bulb tube. 4.1 g of 4-phenyl-2-trifluoromethyl-1,2-pentanediol, boiling
 point 120.degree. C./0.04 hPa, is obtained.
 4.25 g of 4-phenyl-2-trifluoromethyl-1,2-pentanediol in 30 ml of pyridine
 is mixed at 0.degree. C. with 3.8 g of 4-toluenesulfonic acid chloride.
 After 16 hours at 0.degree. C., it is concentrated by evaporation in a
 vacuum, mixed with ethyl acetate, washed with water, dried (Na.sub.2
 SO.sub.4) and concentrated by evaporation. By crystallization from ethyl
 acetate/hexane, 4.9 g of 4-toluenesulfonic
 acid-(2-hydroxy-4-phenyl-2-trifluoromethyl-pentyl)ester, melting point
 95-96.degree. C., is obtained.
 Analogously, 4-toluenesulfonic
 acid-(2-hydroxy-4-methyl-4-phenyl-2-trifluoromethyl-pentyl)ester, melting
 point 78.degree. C., is obtained.
 Analogously, 4-toluenesulfonic
 acid-[4-(4-fluorophenyl)-2-hydroxy-4-methyl-2-trifluoromethyl-pentyl]ester
 , melting point 80-81.degree. C., and 4-toluenesulfonic
 acid-[2-hydroxy-4-(2-methoxy-5-fluorophenyl)-4-methyl-2-trifluoromethyl-pe
 ntyl]ester, melting point 93-95.degree. C., were produced.
 2-(2-Phenylpropyl)-2-trifluoromethyl-oxiran
 400 mg of 4-toluenesulfonic
 acid-(2-hydroxy-4-phenyl-2-trifluoromethyl-pentyl)ester in 5 ml of
 dimethylformamide is mixed at 0.degree. C. with 35 mg of sodium hydride
 (80% in mineral oil). After one hour at 0.degree. C., it is diluted with
 water and extracted with dichloromethane. The dichloromethane phase is
 washed with water, dried (Na.sub.2 SO.sub.4) and concentrated by
 evaporation. The residue is distilled. 200 mg of
 2-(2-phenylpropyl)-2-trifluoromethyl-oxiran, boiling point 110.degree.
 C./1 hPa, is obtained.
 4-Bromo-5-aminophthalide
 23 g of 3-bromo-4-nitro-1,2-xylene is suspended in 200 ml of pyridine and
 600 ml of water and mixed at 60.degree. C. in portions with 260 g of
 potassium permanganate, whereby the temperature rises to 90.degree. C. It
 is heated for 2 more hours to 95.degree. C., filtered, the filtrate is
 acidified with hydrochloric acid and extracted with diethyl ether. After
 the solvent is concentrated by evaporation, 27 g of
 3-bromo-4-nitrophthalic acid is obtained.
 12 g of acid is heated for 15 minutes to 220.degree. C. and then distilled
 on a bulb tube. At 0.03 hPa, 10 g of 3-bromo-4-nitrophthalic acid
 anhydride is distilled.
 The anhydride is dissolved in 120 ml of dimethylformamide and is slowly
 mixed at 0.degree. C. with 78.8 ml of a 0.5 M solution of sodium
 borohydride in dimethylformamide. After 3 hours at 0.degree. C., 2N
 hydrochloric acid is carefully added, and it is extracted with ethyl
 acetate. After washing with potassium bicarbonate solution, drying
 (Na.sub.2 SO.sub.4) and concentration by evaporation of the ethyl acetate
 phase, 6.6 g of 4-bromo-5-nitrophthalide is obtained.
 6.6 g of 4-bromo-5-nitrophthalide is dissolved in 45 ml of ethanol and
 added in drops to a mixture of 65 g of iron(II) sulfate, 220 ml of water
 and 65 ml of ammonia (33%) that is heated to 60.degree. C. and stirred
 well. After 2 hours at 60.degree. C., the mixture is absorptively
 precipitated five times with 200 ml of diethyl ether. The diethyl ether
 phases are concentrated by evaporation. As a residue, 4.1 g of
 4-bromo-5-aminophthalide is obtained, melting point 176-180.degree. C.
 6-Bromo-5-aminophthalide
 4-Bromo-5-nitrophthalic acid anhydride is produced analogously to the
 process of 4-bromo-5-nitro-1,2-xylene that is described above.
 By boiling with ethanol, a mixture of
 2-bromo-6-ethoxycarbonyl-3-nitrobenzoic acid and
 3-bromo-2-ethoxy-carbonyl-4-nitrobenzoic acid is obtained from the above.
 1.2 ml of oxalyl chloride is carefully added in drops to 7.2 ml of a 0.66 m
 solution of dimethylformamide in dichloro-methane at 0.degree. C. The
 solution is stirred for 1 hour at 0.degree. C. and for 5 minutes at room
 temperature. After concentration by evaporation in a vacuum, the residue
 is suspended in 7 ml of acetonitrile, cooled to -35.degree. C. and mixed
 drop by drop with 1.5 g of the ester mixture. After one hour at the same
 temperature, it is cooled to -70.degree. C., and 2.4 ml of a 2 m solution
 of sodium borohydride in dimethylformamide is added in drops. It is
 stirred for 20 hours at room temperature, water is added, alkalized with
 potassium carbonate and extracted with diethyl ether. The diethyl ether
 phase is dried (Na.sub.2 SO.sub.4) and concentrated by evaporation. A
 mixture of 5-bromo-6-nitrophthalide and 6-bromo-5-nitrophthalide, which is
 separated on silica gel with hexane/ethyl acetate (95:5), is obtained.
 The reduction to aminophthalide is carried out as described above.
 6-Bromo-5-aminophthalide, melting point 235-241.degree. C., is obtained.
 5-Amino-3-(1-propenyl)-phthalide
 5 g of 2-bromo-4-nitrobenzoic acid is converted into acid chloride, which
 is dissolved in 50 ml of tetrahydrofuran and added in drops to 3 ml of
 allylamine in 20 ml of tetrahydro-furan, by 2 hours of boiling with 30 ml
 of thionyl chloride and distilling-off of excess thionyl chloride. After
 20 hours at room temperature, it is dispersed between 1N hydrochloric acid
 and ethyl acetate, the ethyl acetate phase is washed with water, dried
 (Na.sub.2 SO.sub.4) and concentrated by evaporation. The residue is
 crystallized with hexane. 5.6 g of 2-bromo-4-nitrobenzoic acid-allylamide,
 melting point 98-100.degree. C., is obtained.
 This material is dissolved in 35 ml of ethanol and added in drops to a
 mixture of 50 g of iron(II) sulfate, 170 ml of water and 50 ml of ammonia
 (33%) that is heated to 60.degree. C. and stirred well. After 2 hours at
 60.degree. C., the mixture is absorptively precipitated 5 times with 200
 ml of diethyl ether, the diethyl ether phases are concentrated by
 evaporation, and the residue is crystallized with hexane. 3.1 g of
 4-amino-2-bromo-benzoic acid-allylamide, melting point 115-117.degree. C.,
 is obtained.
 11 g of 4-amino-2-bromobenzoic acid-allylamide, 5.2 ml of acetonylacetone
 and 200 mg of 4-toluenesulfonic acid are refluxed for 1.5 hours with a
 water separator. Then, the solution is diluted with ethyl acetate, washed
 with 1N hydrochloric acid and then with potassium carbonate solution,
 dried (Na.sub.2 SO.sub.4) and concentrated by evaporation. The residue is
 crystallized with hexane. 13.4 g of
 N-allyl-2-bromo-4-(2,5-dimethylpyrrol-1-yl)-benzamide, melting point
 136-138.degree. C., is obtained.
 3 g of N-allyl-2-bromo-4-(2,5-dimethylpyrrol-1-yl)-benzamide in 100 ml of
 dimethoxyethane is mixed at -70.degree. C. with 14.2 ml of 1.4 M
 butyllithium in hexane. After 30 minutes at -70.degree. C., 1.63 ml of
 crotonaldehyde is added. The solution is allowed to heat to room
 temperature, stirred for another 20 hours, 50 ml of 50% acetic acid is
 added and heated for 6 hours to 60.degree. C. Then, it is diluted with
 water, extracted with ethyl acetate, the ethyl acetate phase is washed
 with potassium carbonate solution. The ethyl acetate phase is dried
 (Na.sub.2 SO.sub.4) and concentrated by evaporation. After chromatography
 on silica gel with hexane ethyl acetate (98:2), the residue produces 1.1 g
 of crystalline 5-(2,6-dimethyl-pyrrol-1-yl)-3-(1-propenyl)-phthalide,
 melting point 91-95.degree. C.
 1.1 g of 5-(2,5-dimethylpyrrol-1-yl)-3-(1-propenyl)-phthalide, 8.56 g of
 hydroxylamine-hydrochloride and 4.58 g of potassium hydroxide in 75 ml of
 ethanol/water (16:6,8, vv) are heated for 24 hours at 120.degree. C. The
 solvent is distilled off, the residue is mixed with water and extracted
 with ethyl acetate. The ethyl acetate phase is dried (Na.sub.2 SO.sub.4)
 and concentrated by evaporation and chromatographed on silica gel. 640 mg
 of 5-amino-3-(1-propenyl)-phthalide, melting point 125-130.degree. C., is
 obtained with dichloromethane/methanol (99:1).
 The phthalides of Table 4 are obtained analogously.
 TABLE 4
 ##STR16##
 X.sup.3a /X.sup.3b Melting Point [.degree. C.]
 CH.sub.3 /H 152-155
 CH.sub.3 /CH.sub.3 94-97
 C.sub.2 H.sub.5 /H 137-140
 C.sub.2 H.sub.5 /C.sub.2 H.sub.5 95-96
 CH.dbd.CH.sub.2 /H 89-93
 --(CH.sub.2).sub.4 -- 105-110
 Analogously to the production of
 4-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide, the compounds
 of Tables 5 and 6 are obtained.
 TABLE 5
 ##STR17##
 Z.sup.n Melting Point
 Example Z .noteq. H (.degree. C.)
 Z.sup.2 = I 205-207
 Z.sup.3 = Cl 170-171
 Z.sup.3 = Br 168-169
 Z.sup.3 = I 155-157
 4-Bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide
 412 mg of 4-methyl-4-phenyl-2-oxovaleric acid is dissolved in 10 ml of
 dimethylacetamide and mixed under argon at -8.degree. C. with 261 mg of
 thionyl chloride. After 20 minutes of stirring at -3 to +3.degree. C., 228
 mg of 4-bromo-5-aminophthalide is added. It is stirred for 1.5 hours at
 room temperature, then mixed with water, extracted with ethyl acetate, the
 organic phase is washed with water, dried (Na.sub.2 SO.sub.4) and after
 the solvent is concentrated by evaporation and after treatment with
 diethyl ether, 360 mg of
 4-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide, melting point
 150-152.degree. C., is obtained.
 5-[3-(1-Phenyl-cyclopropyl)-2-oxo-propionylamino]-phthalide
 was obtained analogously to the process that is described for
 4-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide from
 5-aminophthalide and 3-(1-phenyl-cyclopropyl)-2-oxo-propionic acid,
 melting point 132-138.degree. C.
 5-[3-(1-Phenyl-cyclobutyl)-2-oxo-propionylamino]-phthalide
 was obtained analogously to the process that is described for
 4-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide from
 5-aminophthalide and 3-(1-phenyl-cyclobutyl)-2-oxo-propionic acid, melting
 point 142-146.degree. C.
 5-[3-(1-Phenyl-cyclohexyl)-2-oxo-propionylamino]-phthalide
 was obtained analogously to the process that is described for
 4-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide from
 5-aminophthalide and 3-(1-phenyl-cyclohexyl)-2-oxo-propionic acid, melting
 point 120-123.degree. C.
 The compounds of Table 6 were also produced:
 TABLE 6
 ##STR18##
 Z.sup.n Melting Point
 Example n (.noteq. H) (.degree. C.)
 1 3-F 142-146
 1 2-Cl 148-151
 1 4-Cl 161-170
 1 2-Br 172-178
 1 3-Br 152-159
 1 2,4-Cl.sub.2 135-138
 1 3-OCH.sub.3 140-153
 1 3-CF.sub.2 166-170
 3 140-144
 3 4-CH.sub.3 oil
 4 4-OCH.sub.3 129-130
 6-[3-(1-Phenyl-cyclopropyl)-2-oxo-propionylamino]-4-methyl-2,3-benzoxazin-1
 -one
 was obtained analogously to the process that is described for
 4-bromo-6-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide from
 6-amino-4-methyl-2,3-benzoxazin-1-one and
 3-(1-phenyl-cyclopropyl)-2-oxo-propionic acid, melting point
 197-200.degree. C.
 6-[3-(1-Phenyl-cyclobutyl)-2-oxo-propionylamino]-4-methyl-2,3-benzoxazin-1-
 one
 was obtained analogously to
 6-[3-(1-phenyl-cyclopropyl)-2-oxo-propionylamino]-4-methyl-2,3-benzoxazin-
 1-one using 3-(1-phenyl-cyclobutyl)-2-oxo-propionic acid, melting point
 155-156.degree. C.
 6-[3-(1-Phenyl-cyclohexyl)-2-oxo-propionylamino]-4-methyl-2,3-benzoxazin-1-
 one
 was obtained analogously to
 6-[3-(1-phenyl-cyclopropyl)-2-oxo-propionylamino]-4-methyl-2,3-benzoxazin-
 1-one using 3-(1-phenyl-cyclohexyl)-2-oxo-propionic acid, melting point
 132-134.degree. C.
 6-(4,4-Dimethyl-2-oxo-5-hexenoylamino)-phthalide
 was obtained analogously to the process that is described for
 4-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide from
 5-aminophthalide and 4,4-dimethyl-2-oxo-5-hexenoic acid, melting point
 103-104.degree. C.
 6-Bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide
 Analogously to the example above, 1.7 g of
 6-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide is obtained
 from 2.0 g of 4-methyl-4-phenyl-2-oxovaleric acid and 1.11 g of
 6-bromo-5-aminophthalide with 1.27 g of thionyl chloride in 60 ml of
 dimethylacetamide, melting point 148-150.degree. C.
 5-[4-(4-Iodo-2-methoxyphenyl)-4-methyl-2-oxo-valeroylamino)-phthalide
 was obtained analogously to the process that is described for
 4-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide from
 5-aminophthalide and 4-(4-iodo-2-methoxyphenyl)-4-methyl-2-oxo-valeric
 acid as a foam.
 5-[4-(4-Iodophenyl)-4-methyl-2-oxo-valeroylamino)-phthalide
 was obtained analogously to the process that is described for
 4-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide from
 5-aminophthalide and 4-(4-iodophenyl)-4-methyl-2-oxo-valeric acid as an
 oil.
 5-[4-(3-Iodophenyl)-4-methyl-2-oxo-valeroylamino)-phthalide
 was obtained analogously to the process that is described for
 4-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide from
 5-aminophthalide and 4-(3-iodophenyl)-4-methyl-2-oxo-valeric acid, melting
 point 160-161.degree. C.
 5-[4-(4-Bromo-2-methoxyphenyl)-2-oxo-valeroylamino)-phthalide
 was obtained analogously to the process that is described for
 4-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide from
 5-aminophthalide and 4-(4-bromo-2-methoxyphenyl)-2-oxo-valeric acid,
 melting point 136-140.degree. C.
 5-[3-(1-Phenyl-cyclopentyl)-2-oxo-propionylamino]-phthalide
 was obtained analogously to the process that is described for
 4-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide from
 5-aminophthalide and 3-(1-phenyl-cyclopentyl)-2-oxo-propionic acid,
 melting point 140-144.degree. C.
 6-[4-(5-Fluoro-2-methoxyphenyl)-4-methyl-2-oxo-valeroylamino)-4-methyl-2,3-
 benzoxazin-1-one
 was obtained analogously to the process that is described for
 4-bromo-5-94-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide from
 4-methyl-2,3-benzoxazin-1-one and
 4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxo-valeric acid, melting point
 171-173.degree. C.
 6-[4-(5-Fluoro-2-methoxyphenyl)-4-methyl-2-oxo-valeroylamino)-4-ethyl-2,3-b
 enzoxazin-1-one
 was obtained analogously to the process that is described for
 4-bromo-5-(4-methyl-2-oxo-4-phenyl-valeroylamino)-phthalide from
 4-ethyl-2,3-benzoxazin-1-one and
 4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxo-valeric acid, melting point
 157-158.degree. C.
 6-Amino-4-methyl-2,3-benzoxazin-1-one
 60 g of 2-methyl-5-nitroacetophenone, 38.5 g of
 2,2-dimethyl-1,3-propanediol and 6 g of p-toluenesulfonic acid are boiled
 in 1 l of toluene with a water separator until water is no longer
 produced. The solution is washed with potassium bicarbonate, dried
 (Na.sub.2 SO.sub.4) and concentrated by evaporation. 71.7 g of the
 crystalline ketal is obtained from pentane.
 The latter is oxidized in 1.5 l of pyridine and 4.5 l of water with 350 g
 of potassium permanganate, as described above in the production of
 4-bromo-5-aminophthalide. 56.4 g of
 4-nitro-2-(2,5,5-trimethyl-1,3-dioxan-2-yl)-benzoic acid is obtained.
 52 g of the acid is hydrogenated in 500 ml of methanol and 500 ml of ethyl
 acetate with 10 g of palladium/carbon (10%). 45.5 g of the crystalline
 amino compound is obtained from pentane.
 10 g of the amine is refluxed with 100 ml of concentrated hydrochloric acid
 for 2 hours. The solvent is concentrated by evaporation in a vacuum, and
 the residue is refluxed with 15.7 g of hydroxylamine hydrochloride, 8.4 g
 of potassium hydroxide, 120 ml of ethanol and 50 ml of water for 12 hours.
 It is diluted with water, and the crystals are suctioned off. After
 drying, 3.5 g of 6-amino-4-methyl-2,3-benzoxazine-1-one, melting point
 291-296.degree. C., is obtained.
 6-Amino-4-ethyl-2,3-benzoxazin-1-one
 is obtained analogously from 2-methyl-5-nitropropiophenone, melting point
 89-93.degree. C.
 6-Amino-1-methyl-1-benzotriazole
 is described in Heterocycles 36, 259 (1993).
 5-Amino-benz[1,2,5]oxadiazole
 is described in Boll. Sci. Fac. Chim. Ind. Bologna, 22, 33, 36, 37 (1964).
 5-Amino-benz[1,2,5]-thiazole
 is described in J. Heterocycl. Chem. 11, 777 (1974).
 5-Amino-1-indanone
 is described in J. Org. Chem. 27, 70 (1962).
 6-Amino-1,2,3,4-tetrahydro-1-naphthalinone
 is described in J. Org. Chem. 27, 70 (1962).
 6-Amino-3,4-dihydro-1H-2-benzopyran-1-one
 is produced by catalytic hydrogenation (palladium/carbon) in ethanol from
 the corresponding nitro compound (Canad. J. Chem. 61, 2643 (1983).
 The examples below are used for a more detailed explanation of the
 invention. Other compounds can be produced by using homologous/analogous
 reagents. The required starting compounds are described above under
 "Starting Compounds."