Patent EP-1757608-A1 (EP)
Inventor: CZOLLNER LASZLO
IPC: C07D491/056
Filed: 1997-04-21
Abstract: Benzofuro[3a,3,2,ef][2]benzazepines (I), their ring-opened form (II) and diazabicycloalkanes (III) as well as their enantiomers and addition salts are new: Z = N; or N+ if both R6 and R7 are present and if R7 = O-; R1, R2 = H; F; Cl; Br; I; CN; NC; OH; SH; NO2; SO3H; NH2; NH2; CF3; 1-6C (sic) optionally substituted (ar)alkyl or (ar)alkoxy; NH2 optionally mono- or disubstituted by 1-6C (Ar)alkyl, (Ar)alkylcarbonyl or (Ar)alkoxycarbonyl; COOH; COO(Ar)alkyl; CONH; CON(Ar)alkyl; -(CH2)n-Q; n = 1-3; Q = Cl; Br; OH; COOH; CN; or NC; or R1+R2 = -CH=CH-CH=CH- or -O-(CH2)n-O-; R3 = R1, especially OH or OMe; or R2+R3 = -O-(CH2)n-O-; R4, R5 = either both H; or, alternatively, each combination of H, (ar)alkyl, (ar)alkenyl or (ar)alkynyl with the following: SR8; SOR8; SO2R8; OH (optionally with a protecting group, e.g. TMS, TBDMS); OCSNR8; OCONR9; OCOR8, especially of formula (a): or, when R4 or R5 is other than H, the other may be OH; or R4+R5 = a group of formula =N-NH-R10; =N-NR10R11; or =N-O-R11; or a N-NH-C(=Y1)-Q1; L = -CH2-COOBn; -CH2-SMe; or Ph; R8 = H or 1-10C optionally substituted (ar)alkyl; R9 = -CO-NH-C*(H)(Me)-Ph (where * indicates an optically active centre, the Me being depicted in alpha or beta configurations); R10 = H; 1-6C optionally substituted (ar)alkyl, (ar)alkylcarbonyl or (ar)alkylcarbonyloxy; or a sulphonic acid group, e.g. tosyl or mesyl; R11 = R10 except (Ar)alkylcarbonyloxy; Q1 = Y2 or COOR8; Y1, Y2 = O; S; NH; or NR10 (any spare valencies = H); G1, G2 = -C(R13R14)- or G1+G2 = 3-9C cycloalkan-(1,2)-diyl; R13, R14 = H; OH; lower optionally substituted (ar)alkyl, aryl, (ar)alkoxy or aryloxy or R13+R14 = a 3-7C spiro ring; m = 1-7; G3 = CH2 or CO; R6 = -(G4)p-(G5)q-G6; p, q = 0 or 1; G4 = (CH2)r, C(R15R16)-(CH2)r, O, NR15, or a group of formula (f), (g) or (h): r = 1-6; R15, R16 = H; or lower optionally substituted (ar)alkyl, cycloalkyl or aryl; s = 1-4; t = 0-4; G7 = NR15, O or S; G5 = G4; or S when p = 1; G6 = CHO; COOR17; CONHR17; lower optionally substituted (Ar)alkyl, (Ar)alkenyl, (Ar)alkynyl, cycloalkyl or aryl; OR17; NR17R18; phthalimido; CN; NC; or a group of formula (i)-(k): R17-R20 = H; lower optionally substituted (Ar)alkyl, cycloalkyl or aryl; or R17+R18 or R19+R20 = a 3-8 ring C cycloalkyl; G8 = O; S; NH; NR21; or -(CH2)n-; R21 = CHO; COOR17; aryl or heteroaryl (preferably 2- or 4-pyridyl or 2-pyrimidinyl) optionally substituted by 1 or more F, Cl, Br, I, NO2, NH2, OH, alkyl, alkoxy, CN, NC, CF3, CHO, COOH, COOalkyl, SO3H, SH or S-alkyl; or methyl mono-, di- or trisubstituted by Ph (optionally substituted by 1 or more F, Cl, Br, I, NO2, NH2, alkyl, alkoxy, CN, NC or CF3); R7 = R6 or O- or free electron pair; or R6+R7 = a 3-8 membered ring; R22 = (hetero)aryl optionally with the same substituents as the heteroaryl group R21; or methyl disubstituted by phenyl (optionally with the same substituents as the heteroaryl group R21); R23 = -(G5)q-(G4)p-G9; G9 = H; F; Cl; Br; I; OH; OTs; OMs; O-triflate; COOH; COCl; CHO; OR17; NR17R18; phthalimido; CN; NC; or a group suitable for nucleophilic substitutions or addition or condensation reactions, etc.; X = (if present) inorganic or organic acid ion.