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and diazidomethane) The organic layer was washed with brine (5 × 100 mL), dried with Na2SO4 and
concentrated to provide the azide 12b as a colourless solid (902 mg, 99%), which was deemed
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sufficiently pure by H NMR spectroscopy for use in the next step. Mp: 104.6–106.2 °C. IR (ATR):
3366 s, 2104 s, 1640 s, 1593 s, 1499 s, 1441 s, 1248 s, 1199 s, 848 m, 770 m cm−1. 1H NMR (400 MHz,
CDCl3): δ 7.82–7.79 (m, 2H), 7.76 (bs, 1H), 7.35–7.27 (m, 3H), 7.06–7.00 (m, 4H), 6.97–6.93 (m, 2H),
6.74 (dt, J = 7.0, 2.2 Hz, 1H), 4.11 (t, J = 6.3 Hz, 2H), 3.53 (t, J = 6.3 Hz, 2H), 2.08 (quin, J = 6.3 Hz,
2H). 13C NMR (100 MHz, CDCl3): δ 165.3, 161.9, 159.1 (d, J = 240.5 Hz), 158.6, 152.7, 139.7, 130.3,
129.1, 127.3, 121.0 (d, J = 8.4 Hz), 116.5 (d, J = 23.2 Hz), 114.8, 114.7, 114.2, 110.2, 65.0, 48.3, 28.9.
19F NMR (376 MHz, CDCl3): δ −120.2. LRMS (APCI): m/z 407.2 [M + H]+ (100%). HRMS (APCI):
m/z calcd. For C22H20FN4O3 [M + H]+: 407.1514, found: 407.1514.
4-(3-Aminopropoxy)-N-(3-(4-fluorophenoxy)phenyl)benzamide (5b)
A solution of the azide 12b (100 mg, 0.25 mmol), 10% Pd/C (12 mg) and hydrazine monohydrate
(30 µL, 30 mg, 0.62 mmol) in MeOH (3 mL) were vigorously stirred under a N2 atmosphere at room
temperature. After 20 mins, the reaction mixture was filtered through Celite™ and concentrated to
provide the amino compound 5b as a colourless oil in a quantitative crude conversion. IR (ATR): 3280
br s, 1647 s, 1597 m, 1540 m), 1484 s, 1244 s, 1195 s, 837 s, 779 s, 760 s, 684 s cm−1.1H NMR (400 MHz,
CD3OD): δ 7.90–7.87 (m, 2H), 7.45 (t, J = 2.0 Hz, 1H), 7.39 (ddd, J = 8.0, 2.1, 1.0 Hz, 1H), 7.31
(t, J = 8.0 Hz, 1H), 7.13–7.01 (m, 6H), 6.73 (ddd, J = 8.0, 2.1, 1.0 Hz, 1H), 4.13 (t, J = 6.6 Hz, 2H),
2.84 (br t, J = 6.6 Hz, 2H), 1.96 (quin, 6.6 Hz, 2H). 13C NMR (100 MHz, CD3OD): δ 168.4, 163.5,
160.3 (d, J = 238.9 Hz), 159.5, 154.3, 141.6, 130.9, 130.6, 128.0, 121.9 (d, J = 8.3 Hz), 117.3 (d,
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J = 23.5 Hz), 116.7, 115.3, 114.9, 112.0, 67.3, 39.6, 33.0. F NMR (376 MHz, CD3OD): δ −120.5.
LRMS (APCI): m/z 380.2 [M]+ (100%), 381.2 [M + H]+ (41%). HRMS (APCI): m/z calcd. For
C22H21FN2O3 [M]+: 380.1532, found: 380.1531.
N-(3-(4-Fluorophenoxy)phenyl)-4-(3-guanidinopropoxy)benzamide hydrochloride (6b)
The guanidinylated compound 6b was synthesised according to a modified procedure by
Bernatowicz et al. [38]. The amine 5b (47 mg, 0.12 mmol), DIPEA (35 µL, 26 mg, 0.20 mmol),
1H-pyrazole-1-carboximidine hydrochloride 27 (25 mg, 0.17 mmol) and DMF (2 mL) were added to a
flask and stirred vigorously under a nitrogen atmosphere at room temperature. After 18 h, the solvent
was removed in vacuo to yield the guanidinylated compound 6b as a colourless solid in quantitative
conversion. IR (ATR): 3244 br s, 3150 br s, 1651 s, 1592 s, 1503 s, 1479 s, 1249 s, 1210 m, 1171 s,
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826 m, 791 m, 692 m cm−1. H NMR (400 MHz, CD3OD): δ 7.92–7.88 (m, 2H), 7.47 (t, J = 2.2 Hz,
1H), 7.41 (ddd, J = 8.1, 2.2, 0.9 Hz, 1H), 7.30 (t, J = 8.1 Hz, 1H), 7.11–7.01 (m, 6H), 6.72 (ddd,
J = 8.1, 2.2, 0.9 Hz, 1H), 4.16 (t, J = 6.3 Hz, 2H), 3.42 (t, J = 6.3 Hz, 2H), 2.09 (quin, J = 6.3 Hz, 2H).
13C NMR (100 MHz, CD3OD): 168.3, 163.2, 160.3 (d, J = 239.0 Hz), 159.9, 158.8, 154.3, 141.6,
130.9, 130.7, 128.4, 121.9 (d, J = 8.4 Hz), 117.3 (d, J = 23.3 Hz), 116.7, 115.3, 115.0, 112.0,
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66.3, 39.6, 29.6. F NMR (376 MHz, CD3OD): δ −120.5. LRMS (APCI): m/z 422.2 [M]+ (32%),
381.2 [M − CHN2]+ (35%), 380.2 [M − CH2N2]+ (100%). HRMS (APCI): m/z calcd. For C23H23FN4O3
[M]+: 422.1749, found: 422.1749.