MedChemComm
Page 18 of 18
DOI: 10.1039/C6MD00450D
Hz, 1H,Hꢀ2), 6.49 (d, J = 8.0 Hz, 1H,Hꢀ1), 5.75 (s, 1H,Hꢀ7), 5.65 (d, J = 9.8 Hz, 1H,Hꢀ8), 4.77 (s,
1H,Hꢀ5), 4.55 (d, J = 5.7 Hz, 1H,Hꢀ6), 3.37 (s, 1H,Hꢀ9), 3.09 (s, 1H, amide ꢀNH), 3.01 (d, J = 18.4
Hz, 1H,Hꢀ10), 2.60 (dd, J = 14.7, 7.8 Hz, 1H), 2.42 (s, 1H,ꢀNꢀCH3), 2.33 (d, J = 12.8 Hz, 1H), 2.10 –
1.98 (m, 1H), 1.72 (d, J = 12.1 Hz, 0H), 1.37 – 1.19 (m, 1H), 1.04 (dd, J = 18.9, 11.8 Hz, 1H).13C (150
MHz, CD3OD):δ= 165.97, 149.43, 143.90, 142.22, 140.49, 128.78, 128.54, 125.46, 121.82, 121.01,
119.67, 117.61, 91.43, 75.21, 51.22, 46.17, 42.27, 32.48, 30.26, 24.96, 17.13. Yield:87%,mp: 160ꢀ
162 ̊
C MS: calc: 390.1817, found: HRꢀMS [M+ H+]390.1800, C23H23N3O3
Nꢀ(6ꢀdezoxymorphineꢀ6βꢀyl)nicotinamide: (9d)1HꢀNMR (600 MHz, CDCl3):δ= 9.14 (s, 1H,Arꢀ
H), 8.71 (d, J = 4.5 Hz, 1H,ArꢀH), 8.14 (d, J = 7.9 Hz, 1H,ArꢀH), 7.38 (dd, J = 7.8, 4.9 Hz, 1H,Arꢀ
H), 6.85 (s, 1H,amide ꢀNH), 6.68 (d, J = 8.1 Hz, 1H,Hꢀ2), 6.52 (d, J = 8.1 Hz, 1H,Hꢀ1), 5.82 – 5.75
(m, 1H,Hꢀ7), 5.69 (d, J = 9.9 Hz, 1H,Hꢀ8), 4.87 (s, 1H,Hꢀ5), 4.53 (t, J = 6.2 Hz, 1H,Hꢀ6), 3.40 (s,
1H,Hꢀ9), 3.23 (d, J = 17.6 Hz, 1H), 3.03 (d, J = 18.5 Hz, 1H,Hꢀ10), 2.93 (dd, J = 14.2, 7.1 Hz, 1H),
2.64 (dd, J = 12.0, 4.1 Hz, 1H), 2.47 (s, 3H,ꢀNꢀCH3), 2.39 (d, J = 6.2 Hz, 1H), 2.36 (d, J = 5.6 Hz,
1H), 2.12 (td, J = 12.5, 4.8 Hz, 1H), 1.79 (d, J = 11.0 Hz, 1H).13C (150 MHz, CDCl3):δ= 165.34,
151.96, 147.77, 143.89, 138.83, 135.50, 132.70, 129.65, 129.57, 127.98, 125.45, 124.03, 119.60,
117.39, 92.78, 58.99, 51.79, 47.04, 45.85, 44.51, 43.09, 35.26, 20.45.Yield:80%,mp: 127ꢀ129
̊C MS:
calc: 390.1817, found: HRꢀMS [M+ H+]390.1825, C23H23N3O3
Nꢀ(6ꢀdezoxyꢀ7,8ꢀdihydromorphineꢀ6βꢀyl)isonicotinamide (9e): 1HꢀNMR (600 MHz,
CD3OD):δ= 8.71 (d, J = 6.1 Hz, 1H,ArꢀH), 7.81 (d, J = 6.1 Hz, 1H,ArꢀH), 6.66 (d, J = 8.1 Hz, 1H,Hꢀ
2), 6.62 (d, J = 8.1 Hz, 1H,Hꢀ1), 4.60 (d, J = 8.0 Hz, 1H,Hꢀ5), 3.79 (ddd, J = 12.6, 7.9, 4.5 Hz, 1H,Hꢀ
6), 3.17 (s, 1H, Hꢀ9), 3.07 (d, J = 18.5 Hz, 1H,Hꢀ10), 2.88 (dd, J = 14.3, 7.2 Hz, 1H), 2.57 (dd, J =
12.2, 4.1 Hz, 1H), 2.48 (dd, J = 18.5, 5.5 Hz, 1H), 2.43 (s, 2H,ꢀNꢀCH3), 2.24 (ddt, J = 11.8, 7.6, 3.9
Hz, 1H), 1.94 – 1.89 (m, 1H), 1.89 – 1.84 (m, 1H), 1.72 – 1.68 (m, 1H), 1.64 (dd, J = 13.2, 2.8 Hz,
1H), 1.49 – 1.44 (m, 1H), 1.16 – 1.12 (m, 1H).13C (150 MHz, CD3OD):δ= 165.97, 149.43, 142.79,
141.67, 140.80, 129.33, 124.59, 121.26, 119.05, 117.38, 91.98, 71.02, 59.86, 52.02, 46.17, 43.08,
41.98, 34.46, 28.29, 23.86, 19.66. Yield:88%,mp: 196ꢀ198
̊C MS: calc: 392.1973, found: HRꢀMS
[M+ H+]392.1983, C23H25N3O3
Nꢀ(6ꢀdezoxyꢀ7,8ꢀdihydromorphineꢀ6βꢀyl)nicotinamide (9f): 1HꢀNMR (600 MHz,
CD3OD):δ= 9.01 (s, 1H,ArꢀH), 8.70 (d, J = 4.8 Hz, 1H,ArꢀH), 8.27 (d, J = 7.9 Hz, 1H,ArꢀH), 7.57
(dd, J = 7.9, 5.0 Hz, 1H,ArꢀH), 6.67 (d, J = 8.0 Hz, 1H,Hꢀ2), 6.63 (d, J = 8.3 Hz, 1H,Hꢀ1), 4.61 (d, J
= 7.9 Hz, 1H,Hꢀ5), 3.83 – 3.77 (m, 1H,Hꢀ6), 3.17 (s, 1H,Hꢀ9), 3.07 (d, J = 18.4 Hz, 1H,Hꢀ10), 2.60 –
2.55 (m, 1H), 2.49 (dd, J = 18.3, 5.3 Hz, 1H), 2.44 (s, 2H,ꢀNꢀCH3), 2.25 (dd, J = 12.0, 7.8 Hz, 2H),
1.70 (d, J = 11.4 Hz, 1H), 1.65 (d, J = 10.3 Hz, 1H), 1.50 – 1.43 (m, 1H), 1.30 (d, J = 9.6 Hz, 1H),
1.13 (d, J = 7.9 Hz, 1H).13C (150 MHz, CD3OD): δ= 166.22, 151.41, 147.54, 142.79, 140.81, 135.50,
131.08, 129.09, 124.58, 123.48, 118.73, 116.83, 91.67, 67.38, 59.55, 52.34, 45.86, 42.85, 41.74,
34.70, 27.74, 24.10, 19.90.Yield:74%,mp: 181ꢀ184 C
̊ MS: calc: 392.1973, found: HRꢀMS [M+
H+]392.1977, C23H25N3O3
Nꢀ(6ꢀdezoxyꢀ3ꢀmethylꢀmorphineꢀ6βꢀyl)isonicotinamide: (9g) 1HꢀNMR (600 MHz, CDCl3):δ= 8.72
(d, J = 5.7 Hz, 1H,ArꢀH), 7.60 (dd, J = 4.5, 1.5 Hz, 1H,ArꢀH), 6.68 (d, J = 8.2 Hz, 1H,Hꢀ2), 6.57 (d, J
= 8.2 Hz, 1H,Hꢀ2), 6.27 (d, J = 6.8 Hz, 1H,amideꢀNH), 5.92 – 5.87 (m, 1H,Hꢀ7), 5.70 (dd, J = 9.7,
1.7 Hz, 1H,Hꢀ8), 4.88 (s, 1H,Hꢀ5), 4.61 (t, J = 6.4 Hz, 1H,Hꢀ6), 3.86 (s, 1H,ꢀOꢀCH3), 3.37 (dd, J =
5.6, 3.2 Hz, 1H,Hꢀ9), 3.06 (d, J = 18.2 Hz, 1H,Hꢀ10), 2.58 (dt, J = 14.8, 7.4 Hz, 1H), 2.45 (s, 2H,ꢀNꢀ
CH3), 2.39 – 2.36 (m, 1H), 2.35 – 2.32 (m, 1H), 2.05 (td, J = 12.5, 5.0 Hz, 1H), 1.83 (dt, J = 13.2, 6.6
Hz, 1H). 13C (150 MHz, CDCl3):δ= 165.11, 150.30, 146.11, 141.92, 141.16, 133.29, 130.44, 127.99,
126.56, 120.71, 118.49, 114.30, 92.23, 59.31, 56.77, 50.36, 46.73, 46.02, 43.94, 43.03, 40.55, 39.77,
35.56, 19.65. .Yield:89 %,mp: 98ꢀ101 ̊
C MS: calc: 404.1973 found: HRꢀMS [M+ H+] 404.1585,
C24H25N3O3