E
T. Kapti et al.
Paper
Synthesis
13C NMR (100 MHz, CDCl3): δ = 159.2, 154.6, 133.6, 131.6, 126.5,
3-({[(Isopropylamino)carbonyl]amino}methyl)-1H-indole-2-car-
120.3, 119.9, 115.6, 110.7, 95.6, 52.6, 52.5, 33.4.
bonyl Azide (22b)
HRMS: m/z [M + Na]+ calcd for C13H15N3O4Na: 300.0972; found:
300.0955.
Isopropylamine (0.12 mL, 1.49 mmol) was added to a stirred solution
of 20 (300.0 mg, 1.24 mmol) in anhydrous benzene (60 mL) and the
solution was stirred at 25 °C for 30 min. The precipitate was filtered
and washed with benzene (50 mL) to give urea 22b. This material was
used without further purification in the next step.
3-(2-Isocyanato-2-oxoethyl)-1H-indole-2-carbonyl Azide (20)
Compound 17 (300.0 mg, 1.11 mmol) was dissolved in anhydrous
benzene (60 mL) and stirred at 40–42 °C for 48 h. Removal of the sol-
vent under reduced pressure gave 20, which was used without fur-
ther purification in the next step.
Yield: 310.0 mg (83%); white solid.
IR (ATR): 3333, 2138, 1617, 1558, 1455, 1333, 1233, 1189, 1056 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 11.88 (s, 1 H, NH), 7.83 (d,
J4,5 = 8.2 Hz, H-4), 7.43 (d, J7,6 = 8.3 Hz, 1 H, H-7), 7.31 (dd, J6,7 = 8.3 Hz,
J6,5 = 6.9 Hz, 1 H, H-6), 7.09 (dd, J5,4 = 8.2 Hz, J5,6 = 6.9 Hz, 1 H, H-5),
6.04 (t, J = 5.7 Hz, 1 H, NH), 5.73 (s, 1 H, NH), 4.68 (d, J = 5.7 Hz, 2 H,
CH2), 3.65 (oct, J = 6.4 Hz, 1 H, CH), 0.99 (d, J = 6.4 Hz, 6 H, CH3).
13C NMR (100 MHz, DMSO-d6): δ = 165.6, 157.4, 137.2, 127.1, 126.4,
124.6, 124.3, 121.9, 120.4, 112.8, 41.2, 33.2, 23.5.
Yield: 200.0 mg (74%); yellow solid.
IR (ATR): 3319, 2254, 2140, 1651, 1531, 1438, 1335, 1229, 1190,
1049 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 12.20 (br s, 1 H, NH), 7.90 (d,
J4,5 = 8.1 Hz, 1 H, H-4), 7.52 (d, J7,6 = 8.4 Hz, 1 H, H-7), 7.42–7.38 (m,
1 H, H-6), 7.21 (dd, J5,4 = 8.1 Hz, J5,6 = 7.0 Hz, 1 H, H-5), 5.04 (s, 2 H,
CH2).
3-({[(tert-Butylamino)carbonyl]amino}methyl)-1H-indole-2-car-
bonyl Azide (22c)
13C NMR (100 MHz, DMSO-d6): δ = 165.3, 136.8, 128.3, 126.4, 126.3,
124.5, 120.9, 120.5, 119.4, 113.0, 36.4.
tert-Butylamine (0.16 mL, 1.49 mmol) was added to a stirred solution
of 20 (300.0 mg, 1.24 mmol) in anhydrous benzene (60 mL) and the
solution was stirred at 25 °C for 30 min. The precipitate was filtered
and washed with benzene (50 mL) to give urea 22c. This material was
used without further purification in the next step.
1-[(3-{[(Methoxycarbonyl)amino]methyl}-1H-indol-2-yl)carbon-
yl]triaza-1,2-dien-2-ium (21)
Excess MeOH (5 mL) was added to a stirred solution of 20 (300.0 mg,
1.24 mmol) in anhydrous benzene (60 mL) and stirred at 40 °C for 2 h.
The solvent was evaporated to give the crude product, which was
washed with dichloromethane to give 21. This material was used
without further purification in the next step.
Yield: 270.0 mg (69%); white solid.
IR (ATR): 3341, 2136, 1636, 1525, 1433, 1334, 1193, 1062, 739 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 11.87 (s, 1 H, NH), 7.84 (d,
J4,5 = 8.2 Hz, 1 H, H-4), 7.43 (d, J7,6 = 8.4 Hz, H-7), 7.31 (ddd,
J6,7 = 8.4 Hz, J6,5 = 6.9 Hz, J6,4 = 1.0 Hz, 1 H, H-6), 7.10 (ddd, J5,4 = 8.2 Hz,
J5,6 = 6.9 Hz, J5,3 = 0.9 Hz, 1 H, H-5), 5.98 (t, J = 5.8 Hz, 1 H, NH), 5.71 (s,
1 H, NH), 4.65 (d, J = 5.8 Hz, 2 H, CH2), 1.20 (s, 9 H, CH3).
13C NMR (100 MHz, DMSO-d6): δ = 165.5, 157.1, 137.0, 126.8, 126.2,
124.4, 124.1, 121.7, 120.2, 112.6, 49.0, 32.7, 29.3.
Yield: 249.0 mg (73%); brown solid.
IR (ATR): 2919, 2145, 1696, 1653, 1510, 1237, 1198 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 11.90 (s, 1 H, NH), 7.80 (d,
J4,5 = 8.2 Hz, 1 H, H-4), 7.46 (d, J = 5.3 Hz, 1 H, NH), 7.44 (d,
J7,6 = 8.3 Hz, H-7), 7.31 (dd, J6,7 = 8.3 Hz, J6,5 = 6.9 Hz, 1 H, H-6), 7.10
(dd, J5,4 = 8.2 Hz, J5,6 = 6.9 Hz, 1 H, H-5), 4.72 (d, J = 5.7 Hz, 2 H, CH2),
3.52 (s, 3 H, OCH3).
2-Oxo-N-phenyl-1,2,4,9-tetrahydro-3H-pyrimido[4,5-b]indole-3-
carboxamide (23a)
13C NMR (100 MHz, DMSO-d6): δ = 165.5, 156.6, 136.9, 126.8, 126.0,
124.7, 122.1, 121.4, 120.2, 112.6, 51.3, 34.6.
Urea 22a (300.0 mg, 0.897 mmol) was dissolved in anhydrous THF (60
mL) and the solution was heated at reflux for 24 h. The solvent was
evaporated and the crude product was washed with dichloromethane
to give 23a.
3-{[(Anilinocarbonyl)amino]methyl}-1H-indole-2-carbonyl Azide
(22a)
Aniline (0.14 mL, 1.49 mmol) was added to a stirred solution of 20
(300.0 mg, 1.24 mmol) in anhydrous benzene (60 mL) and the solu-
tion was stirred at 25 °C for 30 min. The precipitate was filtered and
washed with benzene (50 mL) to give urea 22a. This material was
used without further purification in the next step.
Yield: 210.0 mg (76%); yellow solid; mp 221–223 °C.
IR (ATR): 3409, 1697, 1593, 1544, 1209, 1129, 736 cm–1
.
1H NMR (400 MHz, DMSO-d6): δ = 11.57 (s, 1 H, NH), 10.84 (s, 1 H,
NH), 10.81 (s, 1 H, NH), 7.55 (d, J = 7.8 Hz, 2 H, ArH), 7.35 (t, J = 7.8 Hz,
2 H, ArH), 7.33–7.26 (m, 2 H, H-4, H-7), 7.09 (t, J = 7.3 Hz, 1 H, ArH),
7.02–6.92 (m, 2 H, ArH), 4.97 (s, 2 H, CH2).
Yield: 250.0 mg (60%); white solid.
IR (ATR): 3327, 2139, 1633, 1595, 1548, 1497, 1455, 1438, 1311, 1231,
1193 cm–1
.
13C NMR (100 MHz, DMSO-d6): δ = 153.8, 152.4, 138.1, 133.8, 131.9,
1H NMR (400 MHz, DMSO-d6): δ = 12.94 (s, 1 H, NH), 8.46 (s, 1 H, NH),
7.87 (d, J4,5 = 8.3 Hz, 1 H, H-4), 7.44 (d, J7,6 = 8.3 Hz, 1 H, H-7), 7.36–
7.30 (m, 3 H, ArH), 7.21–7.17 (m, 2 H, ArH), 7.15–7.11 (m, 1 H, ArH),
6.89–6.89 (m, 1 H, ArH), 6.50 (t, J = 5.8 Hz, 1 H, NH), 4.77 (d, J = 5.8 Hz,
2 H, CH2).
129.01, 128.95, 124.7, 123.4, 119.6, 119.3, 116.1, 111.3, 85.12, 42.6.
HRMS: m/z [M + H]+ calcd for C17H15N4O2: 307.11895; found:
307.12089.
N-Isopropyl-2-oxo-1,2,4,9-tetrahydro-3H-pyrimido[4,5-b]indole-
3-carboxamide (23b)
13C NMR (100 MHz, DMSO-d6): δ = 165.5, 154.9, 140.3, 137.0, 128.6,
126.8, 126.3, 124.6, 123.2, 121.5, 121.0, 120.5, 117.5, 112.7, 32.9.
Urea 22b (300.0 mg, 0.999 mmol) was dissolved in anhydrous THF
(60 mL) and heated at reflux for 24 h. The solvent was evaporated and
the crude product was purified by washing with dichloromethane to
give 23b.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–G