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NEW 1-AZABICYCLO[3.2.2]NONANE DERIVATIVES OBTAINED BY NUCLEOPHILIC …
2-Quinolin-4-yl-6-vinyl-1-azabicyclo [3.2.2] nonan-3-one (9)
1g( 3,4 mmol) compound 7 was oxidized under Swern procedure [7], with
oxalyl chloride (0,88 g) and DMSO (0,53g). After the oxidation, saturated
NaHCO 3 was added, followed by extraction with DCM; the organic layer was
washed with sat. aq. NaHCO 3 and dried over anh. Na 2 SO 4 . After removal of
the solvent the crude product was purified by column chromatography
(PE:MTBE, 1:1) and resulted 0,57 g product (η=57%).H-NMR: (400 MHz,
CDCl 3 ): δ 8,68(d, J=4,5, H-2’); 8,09-8,02(m,H-8’); 7,82-7,76(m,H-5’); 7,62-
7,56(m, H-7’); 7,44-7,32(m,H-6’); 7,05(d, J=4,5, H-3’); 5,74(ddd, J=6,8, 9,8,
17,1, H-10); 4,97-5,03(m, H-11,H-11); 4,02-3,8(m, H-5,OH); 2,37-2,22(m,H-
7); 2,29-2,19(m, H-8); 2,17(m, H-6); 1,74-1,89(m,H-9); 1,59-1,34(m,H-
2).C 19 H 20 N 2 O(292,36): calc. C 78,05%, H 6,89%, N 9,58%; found C
77,87%, H 7,03%, N 9,42%.
2-Quinolin-4-yl-6-vinyl-1-azabicyclo[3.2.2]nonan-3-oxime (11).
The reaction was conducted with 0,2 g(o,6 mmol) ketone(9), hydroxylamine
hydrochloride 0,65g(0,03 mmol) in ethanol and solid NaOH. The reaction
mixture was refluxed for 1 hour and then cooled to rt. The reaction mixture
was diluted with HCl solution. The crystaline product formed was filtered and
dried. The product was disolved in DCM purified by column chromatography
(MTBE:MeOH, 3:1) and resulted 0,07 g product (η=38%).H-NMR: (400 MHz,
CDCl 3 ): δ 8,92(d, J=4,6, H-2’); 8,65(d, J=8,2, H-5’); 8,05(d, J=8,2, H-
8’);7,66-7,58(m, H-7’);7, 44(m, H-6’); 7,31(d, J=4,5 H-3’); 5,92(ddd, J=6,8,
10,5, 17,2, H-10); 5,26-5,17(m,H-11); 4,42(d, J=9,4, 14,3, H=7); 3,9(m,H-2);
3,37-3,27(m, H-7); 2,96-2,81(m,H-8); 2,53-2,43(m, H-8, H-4); 2,31-2,23(m, H-6);
2,11-2,04(m, H4,H5); 2,02-1,92(m, H-9).C 19 H 21 N 3 O(307,38): calc. C 74,23%, H
6,88%, N 13,67%; found C 73,97%, H 6,96%, N 13,48%.
2-Quinolin-4-yl-6-vinyl-1-aza-biciclo[3.2.2]nonan-3-carbonitryl. (12)
O-mesilylcinchonine 6 (1 g, 0,0026 mmol) and 13 ml TFE and KCN(0,52g;
0,008 mmol) was refluxed for 3 days. The reaction mixture was washed
with sat. aq. NaHCO 3 and dried (Na 2 SO 4 ). After removal of the solvent the
crude product was purified by chromatography (ether:MeOH, 9:1) and
result 0,37 g product (η=47%). H-NMR: (400 MHz, CDCl 3 ): δ 8,93(d, J=4,5
Hz, H-8'); 8,15(d, J=8,4 Hz, H-8'); 8,01(d, J=8,4 Hz, H-5'); 7,76-7,71(m, H-
7'); 7,65-7,59(m, H-6'); 7,39(d, J=4,6 Hz, H-3'); 5,97(m, H-10); 5,28-5,14(m,
H-11); 4,80(d, J=11,7 Hz, H-2); 3,60-3,519M, H-3); 3,50-3,40(m, H-80;
3,23-3,13(m, H-8); 2,93-2,84(m, H-7,H-4); 2,56-2,44(m, H-6); 2,30-2,24(m,
H-5); 2,11-1,85(m, H-4, H-9).C 20 H 21 N 3 (303,38): calc. C 79,17%, H 6,97%, N
13,85%; found C 79,28%, H 7,09%, N 13,62%.
2-(2-Quinolin-4-yl)-6-vinyl-1-aza-biciclo[3.2.2]nonan-3-yl) izoindolin -
1,3-dione (13). O-mesilylcinchonine 6 (1 g,0,00 26 mmol), TFE(3 ml), t-
butylamonium hydrogensulphate(0,22g, 0,00085 mmol) and potasium
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