ACCEPTED MANUSCRIPT
8
Tetrahedron
125.0, 124.8, 120.6, 110.9, 57.0, 29.1; HRMS (ESI-TOF): m/z
calcd for C15H15N2O 239.1184, found 239.1167 [M + H]+.
(S)-2,2-Difluoro-1,2,3,5,10,11a-hexahydro-11H-
benzo[e]pyrrolo[1,2-a][1,4]diazepin-11-one (3e). A dry 10 mL
microwave flask equipped with a septum inlet and magnetic
stirring bar was charged with 1c (0.5 mmol), TEA (0.5 mmol)
and DMF (2.0 mL) under nitrogen atmosphere. After 30 min, 1-
bromo-2-(bromomethyl)benzene (2a, 0.5 mmol) was added and
then the mixture was heated to 70 °C for 12 h or MW irradiation
for 45 min. After completion of step-1, Cs2CO3 (1.5 mmol), CuI
(10 mol%) and L-proline (20 mol%) were added and the mixture
was irradiated under MW (pressure 200 psi, power 150 W) at 140
°C. The reaction was monitored by TLC and LCMS. After
completion, the reaction mixture was diluted with EtOAc (30
mL) and washed with cold water (2 x 10 mL). The organic layer
was separated, dried over Na2SO4 and purified using flash
chromatography using EtOAc: hexane (5:5) as eluent to deliver
compound 3e as a white solid: 96 mg, (80% yield); mp: 185–187
8-Methoxy-5,11,12,13-tetrahydro-6H-
dibenzo[b,f][1,5]diazonin-6-one (3i). Compound 3i was prepared
following the general reaction procedure B and purified by flash
column chromatography using EtOAc: hexane (6.5:3.5) as eluent.
1
White solid: 104 mg (78% yield); mp: 125–127 °C; H NMR
(400 MHz, CDCl3) δ 9.00 (s, 1H), 7.86 (d, J = 3.1 Hz, 1H), 7.31–
7.20 (m, 2H), 7.14–7.03 (m, 2H), 6.90–6.83 (m, 1H), 6.43 (d, J =
7.9 Hz, 1H), 5.83 (s, 1H), 3.90 (s, 3H), 3.75 (t, J = 8.2 Hz 2H),
3.19 (t, J = 8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 167.3,
158.1, 150.9, 138.6, 131.5, 130.7, 127.5, 127.1, 124.9, 120.6,
120.4, 114.6, 110.7, 57.5, 55.7, 29.1; HRMS (ESI-TOF): m/z
calcd for C16H17N2O2 269.1290, found 269.1272 [M + H]+.
20
1
°C; [α]D +138 (c 0.13, acetone); H NMR (400 MHz, CDCl3) δ
8.20 (s, 1H), 7.44–7.33 (m, 2H), 7.31–7.20 (m, 1H), 7.06 (d, J =
7.7 Hz, 1H), 3.97 (d, J = 11.4 Hz, 1H), 3.89 (d, J = 8.1 Hz, 1H),
3.63 (d, J = 11.4 Hz, 1H), 3.45–3.34 (m, 1H), 3.18–2.97 (m, 2H),
2.43–2.25 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 170.0, 137.5,
130.5, 129.5, 129.3, 128.7 (t, 1JC-F = 242.4 Hz), 126.2, 121.4,
60.7, 60.4, 54.0, 35.3; HRMS (ESI-TOF): m/z calcd for
C12H13F2N2O 239.0996, found 239.0980 [M + H]+.
8-Methyl-5,11,12,13-tetrahydro-6H-
dibenzo[b,f][1,5]diazonin-6-one (3j). Compound 3j was prepared
following the general reaction procedure B and purified by flash
column chromatography using EtOAc: hexane (6:4) as eluent.
White solid: 89 mg (71% yield); mp: 142–144 °C; 1H NMR (400
MHz, CDCl3) δ 8.73 (s, 1H), 8.12 (s, 1H), 7.38–7.31 (m, 1H),
7.30–7.22 (m, 2H), 7.07 (t, J = 7.4 Hz, 1H), 6.87 (t, J = 7.4 Hz,
1H), 6.48 (d, J = 7.8 Hz, 1H), 5.82 (s, 1H), 3.77 (t, J = 8.1 Hz,
2H), 3.19 (t, J = 8.1 Hz, 2H), 2.43 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 167.9, 150.5, 143.1, 136.6, 134.0, 132.0, 130.9, 129.8,
127.5, 125.1, 125.0, 120.4, 110.7, 57.2, 29.1, 20.9; HRMS (ESI-
TOF): m/z calcd for C16H17N2O 253.1341, found 253.1328 [M +
H]+.
5,7,8,9,10,12-Hexahydrobenzo[e]pyrido[1,2-a][1,4]diazepin-
6(6aH)-one (3f).21 Compound 3f was prepared following the
general reaction procedure A and purified by flash column
chromatography using EtOAc: hexane (8:2) as eluent. White
solid: 83 mg (77% yield); mp: 178–180 °C; 1H NMR (400 MHz,
CDCl3) δ 8.09 (s, 1H), 7.33 (td, J = 7.6, 1.2 Hz, 1H), 7.28–7.24
(m, 1H), 7.18 (td, J = 7.6, 1.2 Hz, 1H), 7.02 (d, J = 7.6 Hz, 1H),
4.07 (d, J = 13.8 Hz, 1H), 3.59 (d, J = 13.8 Hz, 1H), 2.88 (dd, J =
8.3, 3.0 Hz, 1H), 2.82–2.74 (m, 1H), 2.62–2.52 (m, 1H), 1.95–
1.77 (m, 2H), 1.73–1.58 (m, 3H), 1.30–1.18 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 172.7, 138.0, 130.3, 128.8, 128.4, 125.3,
120.6, 60.7, 58.2, 53.9, 27.0, 25.9, 22.3; HRMS (ESI-TOF): m/z
calcd for C13H17N2O 217.1341, found 217.1335 [M + H]+.
8-Chloro-5,11,12,13-tetrahydro-6H-
dibenzo[b,f][1,5]diazonin-6-one (3k). Compound 3k was
prepared following the general reaction procedure B and purified
by flash column chromatography using EtOAc: hexane (6:4) as
eluent. White solid: 98 mg (72% yield); mp: 158–160 °C; 1H
NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 8.27 (d, J = 2.5 Hz, 1H),
7.49 (dd, J = 8.0, 2.5 Hz, 1H), 7.34 (d, J = 8.5 Hz, 1H), 7.31–
7.23 (m, 1H), 7.10 (t, J = 7.4 Hz, 1H), 6.90 (t, J = 7.4 Hz, 1H),
6.51 (d, J = 8.0 Hz, 1H), 5.92 (s, 1H), 3.78 (t, J = 8.1 Hz, 2H),
3.20 (t, J = 8.1 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 166.4,
149.7, 144.1, 133.2, 132.3, 131.7, 131.0, 127.6, 126.4, 125.2,
121.0, 110.9, 57.2, 29.1; HRMS (ESI-TOF): m/z calcd for
C15H1435ClN2O 273.0795, found 273.0775 [M + H]+.
7,8,9,10,12,13-Hexahydro-5H-benzo[e]pyrido[1,2-
a][1,4]diazocin-6(6aH)-one (3g). Compound 3g was prepared
following the general reaction procedure B and purified by flash
column chromatography using EtOAc: hexane (9:1) as eluent.
1
White solid: 70 mg (61% yield); mp: 156–158 °C; H NMR (400
MHz, acetone-d6) δ 8.20 (s, 1H), 7.22–7.09 (m, 3H), 7.06 (d, J =
7.7 Hz, 1H), 3.02–2.92 (m, 1H), 2.81– 2.69 (m, 4H), 2.65–2.52
(m, 2H), 1.65–1.10 (m, 6H); 13C NMR (100 MHz, CDCl3) δ
178.2, 137.1, 136.1, 128.6, 127.0, 127.0, 122.6, 71.6, 57.8, 55.9,
33.2, 30.5, 25.4, 23.6; HRMS (ESI-TOF): m/z calcd for
C14H19N2O 231.1497, found 231.1482 [M + H]+.
7-Fluoro-5,11,12,13-tetrahydro-6H-
dibenzo[b,f][1,5]diazonin-6-one (3l). Compound 3l was prepared
following the general reaction procedure B and purified by flash
column chromatography using EtOAc: hexane (6.5:3.5) as eluent.
White solid: 96 mg (75% yield); mp: 151–153 °C; 1H NMR (400
MHz, CDCl3) δ 7.40–7.32 (m, 1H), 7.31–7.27 (m, 1H), 7.20 (d, J
= 7.3 Hz, 1H), 7.07 (t, J = 7.7 Hz, 1H), 6.96–6.90 (m, 1H), 6.81
(td, J = 7.3, 0.6 Hz, 1H), 6.72 (d, J = 7.7 Hz, 1H), 6.13 (s, 1H),
5,11,12,13-Tetrahydro-6H-dibenzo[b,f][1,5]diazonin-6-one
(3h). Compound 3h was prepared following the general reaction
procedure B and purified by flash column chromatography using
EtOAc: hexane (6:4) as eluent. White solid: 91 mg (76% yield);
5.98 (s, 1H), 3.93 (t, J = 8.5 Hz, 2H), 3.15 (t, J = 8.5 Hz, 2H); 13
C
NMR (100 MHz, CDCl3) δ 166.1, 160.7 (d, 1JC-F = 252.5 Hz),
148.6, 145.2, 131.6, 131.0, 127.1, 125.1, 120.4, 119.8, 118.3,
111.7, 109.8, 55.3, 29.0; HRMS (ESI-TOF): m/z calcd for
C15H14FN2O 257.1090, found 257.1086 [M + H]+.
1
mp: 105–107 °C; H NMR (400 MHz, CDCl3) δ 8.58 (s, 1H),
8.35–8.24 (m, 1H), 7.59–7.50 (m, 1H), 7.38 (t, J = 7.6 Hz, 2H),
7.31–7.21 (m, 1H), 7.09 (t, J = 7.6 Hz, 1H), 6.88 (t, J = 7.3 Hz,
1H), 6.53 (d, J = 7.9 Hz, 1H), 5.83 (s, 1H), 3.82 (t, J = 8.2 Hz,
2H), 3.20 (t, J = 8.2 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
167.8, 150.1, 145.5, 133.2, 131.8, 131.0, 130.2, 127.5, 126.5,
6,11-Dihydro-12H-dibenzo[b,f][1,5]oxazocin-12-one (3m). A
dry 10 mL microwave flask equipped with a septum inlet and