Patent GB-1391234-A (GB)
Title: Indole derivatives
IPC: C07D209/08
Filed: 1973-01-15
Abstract: 1391234 Indole derivatives AYERST Mc- KENNA & HARRISON Ltd 15 Jan 1973 [13 Jan 1972 12 Oot 1972] 2005/73 Heading C2C The invention comprises compounds of the general Formula I in which R<SP>1</SP> is lower alkyl or lower cycloalkyl; R<SP>2</SP> ,  R<SP>3</SP> ,  R<SP>4</SP> and R<SP>5</SP> are the same or different and are hydrogen or lower alkyl; R<SP>6</SP> is hydrogen, lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, nitro or halo; R<SP>7</SP> is hydrogen, lower alkyl, lower alkenyl, propargyl, phenyl (lower) alkyl or a radical of formula -AlkNR<SP>8</SP>R<SP>9</SP> in which Alk is an alkylene group of formula CR<SP>10</SP>R<SP>11</SP>CR<SP>12</SP>R<SP>13</SP>, CR<SP>10</SP>R<SP>11</SP>CR<SP>12</SP>R<SP>13</SP>CR<SP>14</SP>R<SP>15</SP> or CR<SP>10</SP>R<SP>11</SP>CR<SP>12</SP>R<SP>13</SP>CR<SP>14</SP>R<SP>15</SP>CR<SP>16</SP>R<SP>17</SP> in which are hydrogen or lower alkyl and R<SP>8</SP> and R<SP>9</SP> are hydrogen or lower alkyl or together with the nitrogen atom to which they are joined form a 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 1- piperazinyl, 4-(lower alkyl) piperazinyl or 4- [hydroxy (lower)alkyl]-1-piperazinyl; X is O or S; and Y is lower alkyl, phenyl(lower)alkyl or a group -AlkNR<SP>8</SP>R<SP>9</SP> as defined above in which Alk may also be CR<SP>10</SP>R<SP>11</SP>; with the proviso that at least one of R<SP>7</SP> and Y is -Alk-NR<SP>8</SP>R<SP>9</SP>; and the corresponding acid addition salts thereof. The lower alkyl groups referred to are those with 1-6 carbon atoms, the "lower" alkenyl radicals contain 2-6 carbon atoms the phenyl, (lower) alkyl groups are those in which the alkyl group contains 1-4 carbon atoms and the lower cycloalkyi radicals contain 3-6 carbon atoms. The compounds of the invention may be made by reacting a compound of Formula II in which X<SP>1</SP> is hydroxy mercapto, -S-SO 3 Na or S-SO 3 4 with a compound of formula R<SP>1</SP>COZ in which Z is (a) C00R<SP>19</SP> or Alk<SP>1</SP>COOR<SP>19</SP> in which R<SP>19</SP> is hydrogen or lower alkyl and Alk<SP>1</SP> is CR<SP>10</SP>R<SP>11</SP>, CR<SP>10</SP>R<SP>11</SP>CR<SP>12</SP>R<SP>13 </SP>or in which R<SP>10</SP>-R<SP>13</SP> are H or alkyl; (b) CONR<SP>8</SP>R<SP>9</SP> or Alk<SP>1</SP>CONR<SP>8</SP>R<SP>9</SP>; (c) CH 2 OCOR<SP>20</SP> or in which R<SP>20</SP> is H or lower alkyl; (d) Alk<SP>2</SP>L in which Alk<SP>2</SP> is CR<SP>10</SP>R<SP>11</SP>CHR<SP>12</SP>, or CR<SP>10</SP>R<SP>11</SP>CR<SP>12</SP>R<SP>13</SP>CR<SP>14</SP>R<SP>15</SP>CHR<SP>16</SP> in which C<SP>10</SP>-C<SP>16</SP> are H or alkyl and L is halo; (e) AlkNR<SP>8</SP>COR<SP>21</SP> in which AlkR<SP>8</SP> are as defined above and R<SP>21</SP> is H or C 1 -C 5  alkyl; (f) AlkNO 2  (g) lower alkyl or phenyl (lower) alkyl or (h) AIkNR<SP>8</SP>R<SP>9</SP> to give a compound of Formula VII In the case when Z is Alk-NR<SP>8</SP>R<SP>9</SP> the product is the desired product of Formula I; when Z is one of the other groups the compound may be converted to one of the desired products as follows: (a) when Z is COOB<SP>19</SP> or Alk<SP>1</SP>COOR<SP>19</SP>: by hydrolysis of the group Z to the free acid, amidation and reduction and if desired N- alkylation of the indole nitrogen to give compounds in which Y is -AlkNR<SP>8</SP>R<SP>9</SP>; (b) when Z is CONR<SP>8</SP>R<SP>5</SP> or Alk<SP>1</SP>-CONR<SP>8</SP>R<SP>9</SP> by reduction and if desired N-alkylation &C of the indole ring; (c) when Z is CH 2 OCOR<SP>20</SP> or Alk'CH 2 OCOR<SP>20</SP> by hydrolysis to give the corresponding alcohol which is oxidized to the corresponding aldehyde; the aldehyde is reacted with an amine of formula NHR<SP>8</SP>R<SP>9</SP>; the nitrogen in the indole ring may then be substituted as required; (d) when Z is Alk<SP>2</SP>L by treatment with an excess of an amine HNR<SP>8</SP>R<SP>9</SP>; when Z is AIkNR<SP>8</SP>COR<SP>21</SP> by reduction with a complex metal hydride; (f) when Z is Alk-NO 2  by reduction with a complex metal hydride; (g) when Z is lower alkyl or phenyl (lower) alkyl by treatment with an amino (lower) alkyl halide which introduces the group-(Alk)NR<SP>8</SP>R<SP>9</SP> on to the indole nitrogen atom. In cases when R<SP>7</SP> is not a group -Alk-NR<SP>8</SP>R<SP>9</SP> the group R<SP>7</SP> may be introduced into the nitrogen atom of the indole ring at any stage in the process. A very large number examples of preparation of the compounds of the invention and of intermediates therefor are given. The products of the invention are stated to have valuable pharmacological properties.