E
M. C. Bagley et al.
Letter
Synlett
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(29) General Procedure for H/D Exchange of 4-Aminopyridines
A solution of the substrate in D2O (5 mL) was irradiated in a
sealed Pyrex tube at 190 °C for 2 h (hold time) using a CEM
Explorer microwave synthesizer (maximum pressure 150 psi)
by moderation of the initial microwave power (300 W). The
mixture was cooled in a stream of compressed air and extracted
with CH2Cl2 (3 × 10 mL). The organic extracts were combined,
dried (MgSO4), filtered, and evaporated in vacuo.
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(31) See Supporting Information for detailed experimental proce-
dures and characterization data.
4-Aminopyridine-d2 (8a)
Compd 8a was prepared as a colorless solid; mp 157 °C. IR
(neat): 3433, 3144, 3036, 2967, 2262, 1686, 1616, 1583, 1519,
1368, 1299, 1279, 1005, 891, 756 cm–1 1H NMR (500 MHz,
.
CD3OD): δ = 7.95 (0.04 H, d, J = 5 Hz, 2,6-H), 6.55 (1 H, s, 3,5-H).
13C NMR (125 MHz, CD3OD): δ = 155.3 (s, C-N), 148.4 (s, CH iso-
topologue), 148.1 (tD, J = 26 Hz, CD), 108.9 (s, CH). MS (EI): m/z
(%) = 96 (100) [M•+], 69 (25), 41 (35).
4-(Methylamino)pyridine-d2 (10a)
Compd 10a was prepared as a colorless solid; mp 125 °C. IR
(neat): 3396, 3323, 3269, 3030, 2497, 2402, 2232, 1909, 1635,
1564, 1460, 1301, 1250, 1153, 1042, 914 cm–1 1H NMR (500
.
MHz, CD3OD): δ = 7.99 (0.04 H, d, J = 7 Hz, 2,6-H), 6.51 (1.56 H,
s, 3,5-H), 2.80 (3 H, s, Me). 13C NMR (125 MHz, CD3OD): δ =
155.5 (s, CN), 147.9 (tD, J = 27 Hz, CD), 106.7 (s, CH), 27.8 (s, Me).
MS (EI): m/z (%) = 111 (52), 110 (100) [M•+], 109 (69).
4-(Dimethylamino)pyridine-d2 (11a)
Compd 11a (300 mg, 2.45 mmol) was prepared as a colorless
solid; mp 113–114 °C. IR (neat): 3286, 3250, 3179, 3045, 2922,
2819, 2236, 1579, 1498, 1350,1308, 1225, 1068, 993, 750 cm–1
.
1H NMR (500 MHz, CD3OD): δ = 8.06 (0.07 H, m, 2,6-H), 6.63
(1.88 H, s, 3,5-H), 3.03 (6 H, s, 2Me). 13C NMR (125 MHz,
CD3OD): δ = 155.0 (s, CN), 147.7 (tD, J = 25 Hz, CD), 106.3 (s, CH),
37.7 (s, Me). MS (EI): m/z (%) = 124 (86) [M•+], 123 (100), 107 (6),
96 (24), 80 (54), 52 (81), 42 (42). HRMS: m/z [M + H] calcd for
C7H8D2N2: 125.1042; found: 125.1043.
4-Pyrrolidinopyridine-d2 (12a)
Compd 12a (300 mg, 2.02 mmol) was prepared as a colorless
solid; mp 59 °C. IR (neat): 3074, 2961, 2910, 2845, 2230, 1583,
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1532, 1478, 1361, 1286, 1246, 1154, 997, 700 cm–1 1H NMR
.
(500 MHz, CDCl3): δ = 8.20 (0.10 H, d, J = 5 Hz, 2,6-H), 6.36 (1.82
H, s, 3,5-H), 3.29 (4 H, t, J = 6 Hz, 2′,5′-H), 2.02 (4 H, t, J = 6 Hz,
3′,4′-H). 13C NMR (125 MHz, CD3OD): δ = 152.4 (s, CN), 147.5 (tD,
J = 27 Hz, CD), 106.7 (s, CH), 46.7 (s, CH2), 24.8 (s, CH2). MS (EI):
m/z (%) = 150 (85) [M•+], 149 (100), 121 (15). HRMS: m/z [M + H]
calcd for C9H10D2N2: 151.1199; found: 151.1199.
4-Aminoquinoline-d1 (13a)
Compd 13a was prepared as an orange solid; mp 155 °C. IR
(neat): 3443, 2968, 1683, 1528, 1475, 1339, 1316, 1245, 1009,
917, 751 cm–1. 1H NMR (500 MHz, CD3OD): δ = 8.25 (0.11 H, s, 2-
H), 8.06 (0.91 H, d, J = 8 Hz, 5- or 8-H), 7.81 (0.91 H, d, J = 8 Hz,
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–F