Molecules 2019, 24, 772
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(1S,4R,4aR,6aS,12aS)-6-((1-(2-Methylbenzyl)-1H-1,2,3-triazol-4-yl)-methyl)-1,4,4a,6,6a,12a-hexahydro-1,4-
◦
methanoisoindolo[2,1-a]quinazoline-5,11-dione [(
−
)-
7
]: Whit◦e crystals (70% yield), m.p. 100–107 C,
[α]2D0
=
−
20 (c = 0.5, EtOH), 1H-NMR (500 MHz, CDCl3, 30 C):
δ
= 1.31–1.42 (m, 2H, H-13) 2.26 (s, 3H,
CH3), 2.54–2.58 (m, 1H, H-4a) 2.81–2.85 (m, 1H, H-4), 3.17–3.21 (m, 1H, H-1), 4.50–4.54 (m, 1H, H-12a),
4.57–4.64 (d, J = 15.9 Hz, 1H, NCH2), 5.35–5.42 (d, J = 15.9 Hz, 1H, NCH2), 5.53 (s, 2H, NCH2Ar) 6.10 (s,
1H, H-6a), 6.26–6.41 (m, 2H, H-2, H-◦3), 7.03–7.33 (m, 4H, Ar), 7.37 (s, 1H, CHtriazol) 7.52–8.34 (m, 4H,
Ar), 13C NMR (125 MHz, CDCl3, 30 C):
δ = 19.0, 37.5, 41.9, 44.5, 48.6, 49.4, 49.6, 52.4, 68.1, 122.6, 124.4,
126.5, 126.7, 129.2, 129.3, 130.3, 131.0, 131.9, 132.1, 132.4, 136.7, 138.2, 139.6, 144.0, 166.9, 171.5. ppm.
C27H25N5O2 (451.52): calcd. C, 71.82; H, 5.58; N, 15.51; found C 71.93; H 5.47; N 15.35.
(1R,4S,4aS,6aR,12aR)-6-((1-(2-Methylbenzyl)-1H-1,2,3-triazol-4-yl)-methyl)-1,4,4a,6,6a,12a-hex◦ahydro-1,4-
methanoisoindolo[2,1-a]quinazoline-5,11-dione [(+)-7 =
]: White crystals (74% yield), m.p. 100–102 C, [α]2D0
+20 (c = 0.5, EtOH).
(1S,4R,4aS,6aR,12aR)-6-((1-(2-Methylbenzyl)-1H-1,2,3-triazol-4-yl)-methyl)-1,4,4a,6,6a,12a-hexahydro-1,4-
◦
methanoisoindolo[2,1-a]quinazoline-5,11-dione [(
−
)-16]: White crystals (72% yield), m.p. 128–130 C,
[α]2D0
=
−
20 (c = 0.5, EtOH), 1H-NMR (500 MHz, CDCl3, 30 ◦C):
δ
= 1.53–1.65 (m, 2H, H-13) 2.28 (s,
3H, CH3), 3.08 (m, 1H, H-4a) 3.20–3.25 (m, 1H, H-4), 3.28–3.33 (m, 1H, H-1), 4.45–4.55 (m, 1H, H-12a),
5.20–5.29 (m, 2H, NCH2), 5.47 (m, 2H, NCH2Ar) 5.64 (m, 1H, H-3), 5.79 (s, 1H, H-6a), 5.98 (m, 1H, H-2)
◦
7.03–7.32 (m, 4H, Ar), 7.40 (s, 1H, CHtriazol) 7.51–8.40 (m, 4H, Ar), 13C NMR (125 MHz, CDCl3, 30 C):
δ
= 19.0, 37.2, 42.7, 47.8, 48.8, 48.9, 50.0, 52.4, 68.6, 122.9, 124.2, 126.8, 126.8, 129.3, 129.4, 130.0, 131.1,
131.9, 131.9, 132.4, 135.4, 136.7, 137.0, 139.7, 144.0, 167.5, 171.2 ppm. C27H25N5O2 (451.52): calcd. C,
71.82; H, 5.58; N, 15.51; found C 71.91; H 5.43; N 15.32.
(1R,4S,4aR,6aS,12aS)-6-((1-(2-Methylbenzyl)-1H-1,2,3-triazol-4-yl)-methyl)-1,4,4a,6,6a,12a-hexahydro-1,4-
methanoisoindolo[2,1-a]quinazoline-5,11-dione [(+)-16]: White crystals (74% yield), m.p. 97–99 ◦C, [α]2D0
=
+19.3 (c = 0.5, EtOH).
3.2.6. RDA Protocols for the Synthesis of Pyrimido[2,1-a]isoindols [(−)-8 (+)-8, (−)-9, (+)-9]
Isoindoloquinazoline derivatives [(
−
)-
6
, (+)-
6
, (
−
)-
7
, (+)-
7
, (
−
)-15, (+)-15, ( )-16, (+)-16, 0.5 mmol]
−
◦
were dissolved in 5 mL 1,2-dichlorobenzene. The solution was stirred and heated to 220 C for 60 min
at max. 300 W microwave irradiation. Then the solvent was evaporated, the residue was dissolved in
EtOAc and purified by column chromatography on silica gel eluting with EtOAc.
(S)-1-(Prop-2-yn-1-yl)-1,10b-dihydropyrimido[2,1-a]isoindole-2,6-dione [(
m.p. 91–93 ◦C, [α]2D0 376 (c = 0.2, EtOH), 1H-NMR (500 MHz, CDCl3, 30 ◦C):
1H, C CH), 3.73 (dd, J = 17.7, 2.1, 1H,CH2) 5.15 (d, J = 17.7 Hz, 1H, CH2) 5.54 (d, J = 7.6 Hz, 1H, H-3)
6.20 (s, 1H, H-10b) 7.66–8.10 (m, 5H, Ar, H-4), 13C NMR (125 MHz, CDCl3, 30 ◦C):
= 31.3, 69.8, 73.7,
−
)-8
]: White crystals (52% yield),
=
−
δ
= 2.45 (t, J = 2.5 Hz,
≡
δ
79.9, 106.8, 125.4, 125.4, 130.8, 131.7, 133.7, 133.7, 138.5, 164.3, 165.4. ppm. C14H10N2O2 (238.24): calcd.
C, 70.58; H, 4.23; N, 11.76; found C 70.81; H 4.41; N 11.52.
(R)-1-(Prop-2-yn-1-yl)-1,10b-dihydropyrimido[2,1-a]isoindole-2,6-dione [(+)-8]: White crystals (51% yield),
m.p. 93–95 ◦C, [α]2D0 = +368 (c = 0.2, EtOH).
(S)-1-((1-(2-Methylbenzyl)-1H-1,2,3-triazol-4-yl)methyl)-1,10b-dihydropyrimido[2,1-a]isoindole-2,6-dione
]: White crystals (72% yield), m.p. 199–200 C, [α]2D0
=
−
295 (c = 0.2, EtOH), 1H-NMR (500 MHz,
◦
[(
−
)-
9
◦
CDCl3, 30 C):
δ = 2.31 (s, 3H, CH3), 4.45 (d, J = 15.7 Hz, 1H, NCH2CH) 5.15 (d, J = 15.8 Hz, 1H,
NCH2CH) 5.43–5.64 (m, 3H, NCH2Ar, H-3) 6.18 (s, 1H, H-10b) 7.17–7.31 (m, 4H, Ar) 7.55 (1H, s,
◦
CHtriazol) 7.63–7.95 (m, 4H, Ar) 8.70 (d, J = 7.9 Hz 1H, H-4), 13C NMR (125 MHz, CDCl3, 30 C):
δ = 19.1, 37.2, 52.4, 70.3, 106.9, 123.5, 125.0, 126.7, 127.5, 129.2, 129.6, 130.6, 131.1, 131.6, 132.3, 133.6,
133.6, 136.9, 138.9, 143.8, 164.4, 165.8. ppm. C22H19N5O2 (385.42): calcd. C, 68.56; H, 4.97; N, 18.17;
found C 68.71; H 4.81; N 18.39.