3
077
Synthesis
S. Tommasi et al.
Paper
1
3-Amino-N-[2-(methylsulfanyl)ethyl]-2-oxoazetidine-1-carbox-
H NMR (400 MHz, CD OD): δ = 4.61 (dt, J = 47.1 Hz, JH,H = 4.7 Hz, 2
3
H,F
imidamide Trifluoroacetic Acid Salt (7e)
H, FCH ), 3.64 (dd, J = 21.6 Hz, JH,H = 4.7 Hz, 2 H, NCH ), 3.68 (dd,
2
H
,
F
2
J = 5.5, 3.7 Hz, 2 H, CH N), 2.77 (t, J = 6.9 Hz, 2 H, CH ).
General Procedure D; yield: 33 mg (99%); colorless oil.
2
2
13
C NMR (100 MHz, CD OD): δ = 167.8 (C=O), 153.9 (CN ), 81.0 (d,
IR (ATR, neat): 3675, 2972, 2901, 1752 (C=O stretch lactam), 1661,
3
3
JC,F = 168.8 Hz, FCH ), 41.8 (d, J = 20.5 Hz, CH N), 36.7 (NCH ), 29.5
1
527, 1432, 1349, 1250, 1179, 1130, 1066, 1048, 884, 837, 798, 721,
2
C,F
2
2
–1
(CH2).
598, 518, 438 cm
.
19
1
F NMR (376 MHz, CD OD): δ = –225.44 (tt, J = 47.1, 21.6 Hz, 1 F).
3
H NMR (400 MHz, DMSO-d ): δ = 8.25 (br, 2 H, 2 × NH), 7.90 (br, 2 H,
6
+
+
NH ), 3.80 (br, 1 H, CH), 3.71–3.52 (br, 2 H, NCH ), 3.35 (t, J = 6.9 Hz, 2
ESI-MS: m/z [M + H] calcd for C H FN O: 160.1, [2 M + H] calcd for
6 11 3
2
2
+
H, CH N), 2.63 (t, J = 6.9 Hz, 2 H, SCH ), 2.09 (s, 3 H, CH S).
C12H F N O : 319.2; found (%): 160.1 (100, [M + H] ), 319.1 (45, [2 M
2
2
3
21 2 6 2
+
13
+ H] ).
HRMS: m/z [M + H] calcd for C H FN O: 160.0881; found: 160.0885.
C NMR (100 MHz, DMSO-d ): δ = 169.8 (C=O), 156.7 (CN ), 53.0
6
3
+
(
CH), 42.2 (NCH ), 40.8 (CH N), 32.5 (SCH ), 15.0 (CH S).
2 2 2 3
6
11
3
+
+
ESI-MS: m/z [M + H] calcd for C H N OS: 203.1, [2 M + H] calcd for
7
15
4
+
C13
H
N O S : 405.2; found (%): 203.1 (100, [M + H] , 405.1 (80, [2 M
N-(2-Methoxyethyl)-2-oxopyrrolidine-1-carboximidamide (7i)
General Procedure D; yield: 24 mg (99%); colorless oil.
26
+
8
2 2
+
H] ).
+
HRMS: m/z [M + H] calcd for C H N OS: 203.0961; found: 203.0961.
7
15
4
IR (ATR, neat): 3675, 3160, 2988, 2901, 1738 (C=O stretch lactam),
1
661, 1620, 1478, 1461, 1384, 1292, 1169, 1122, 1066, 1028, 943,
–1
2
-Oxo-N-(pent-4-yn-1-yl)azetidine-1-carboximidamide (7f)
831, 797, 718, 705, 593, 518, 428 cm .
1
General Procedure D; yield: 38 mg (98%); colorless oil.
H NMR (400 MHz, D O): δ = 3.82 (t, J = 7.3 Hz, 2 H, NCH ), 3.64–3.58
2 2
(
m, 2 H, CH N), 3.48 (t, J = 5.0 Hz, 2 H, OCH ), 3.32 (s, 3 H, CH O), 2.64
IR (ATR, neat): 3675, 3279, 3087, 2971, 2901, 1735 (C=O stretch lact-
am), 1685, 1659, 1525, 1468, 1433, 1372, 1330, 1278, 1232, 1182,
2
2
3
(t, J = 8.2 Hz, 2 H, CH ), 2.15–2.05 (m, 2 H, CH ).
2
2
–1
13
1131, 1100, 1066, 1057, 879, 837, 798, 721, 640, 518, 498 cm
.
C NMR (100 MHz, D O): δ = 180.8 (C=O), 153.6 (CN ), 69.4 (OCH ),
2 3 2
1
58.3 (CH O), 47.0 (NCH ), 41.5 (CH N), 32.3 (CH ), 16.4 (CH ).
H NMR (400 MHz, DMSO-d ): δ = 9.36 (br, 1 H, NH), 8.57 (br, 1 H,
3 2 2 2 2
6
+
NH), 3.54 (dd, J = 6.5, 4.2 Hz, 2 H, NCH ), 3.32–3.21 (m, 2 H, CH N),
2
J = 7.2, 2.6 Hz, 2 H, CH ), 1.80–1.67 (m, 2 H, CH ).
ESI-MS: m/z [M + H] calcd for C H N O : 186.1; found (%): 186.1
8 16 3 2
2
2
+
.88 (t, J = 2.7 Hz, 1 H, CH), 2.67 (dd, J = 8.3, 5.5 Hz, 2 H, CH ), 2.24 (td,
(100, [M + H] ).
HRMS: m/z [M + H] calcd for C H N O : 186.1237; found: 186.1236.
2
2
2
+
8
16
3
2
13
C NMR (100 MHz, DMSO-d ): δ = 168.7 (C=O), 153.1 (CN ), 83.8 (C),
6
3
7
2.4 (CH), 40.7 (CH N), 36.8 (NCH ), 30.2 (CH ), 27.3 (CH ), 15.5 (CH ).
2 2 2 2 2
3-Amino-N-(2-methoxyethyl)-2-oxopiperidine-1-carboximid-
amide Trifluoroacetic Acid Salt (7j)
+
+
ESI-MS: m/z [M + H] calcd for C H N O: 180.1, [2 M + H] calcd for
9
14
3
+
C18H27N O : 359.2; found (%): 180.1 (100, [M + H] ), 359.3 (58, [2 M +
6
2
General Procedure D; yield: 17 mg (99%); colorless oil.
H]+).
IR (ATR, neat): 3364, 3157, 1716 (C=O stretch lactam), 1671, 1502,
+
HRMS: m/z [M + H] calcd for C H N O: 180.1131; found: 180.1127.
–1
9
14
3
1218, 1173, 1021, 766, 632, 575, 512, 430 cm .
1
H NMR (400 MHz, D O): δ = 4.21(dd, J = 10.9, 5.4 Hz, 1 H, CH), 3.83–
2
3
-Amino-N-(2-methoxyethyl)-2-oxoazepane-1-carboximidamide
3
.66 (m, 2 H, NCH ), 3.62 (s, 2 H, CH N), 3.51 (s, 2 H, OCH ), 3.32 (s, 3
2
2
2
Trifluoroacetic Acid Salt (7g)
H, CH O), 2.44–2.29 (m, 1 H, CH), 2.15–1.97 (m, 2 H, CH ), 1.96–1.82
3
2
General Procedure D; yield: 26 mg (99%); white waxy solid.
(m, 1 H, CH).
13
IR (ATR, neat): 3322, 3095, 1709 (C=O stretch lactam), 1689, 1614,
C NMR (100 MHz, D O): δ = 169.4 (C=O), 155.6 (CN ), 68.9 (NCH ),
2
3
2
1
1
1
564, 1505, 1460, 1435, 1396, 1357, 1278, 1241, 1222, 1184, 1169,
58.3 (CH O), 50.7 (CH), 48.3 (CH N), 42.7 (OCH ), 23.6 (CH ), 19.6
3
2
2
2
–1
120, 1044, 1025, 989, 763, 730, 629, 580, 517, 439 cm
.
(CH2).
ESI-MS: m/z [M + H] calcd for C H N O : 215.2; found (%): 215.2
+
H NMR (400 MHz, D O): δ = 4.48 (dd, J = 10.1, 1.6 Hz, 1 H, CH), 3.85–
2
9
19
4
2
+
3.72 (m, 2 H, NCH ), 3.69–3.61 (m, 2 H, CH N), 3.50–3.54 (m, 2 H,
(100, [M + H] ).
HRMS: m/z [M + H] calcd for C H N O : 215.1503; found: 215.1505.
2
2
CH ), 3.34 (s, 3 H, CH O), 2.09–1.84 (m, 4 H, 2 × CH ), 1.80–1.55 (m, 2
H, CH2).
+
2
3
2
9
19
4
2
1
3
C NMR (100 MHz, D O): δ = 172.2 (C=O), 156.8 (CN ), 68.8 (CH N),
2
3
2
N-Ethyl-2-oxopyrrolidine-1-carboximidamide (7k)
5
2
8.3 (CH ), 54.1 (CH), 49.9 (NCH ), 42.9 (CH ), 27.8 (CH ), 26.8 (CH ),
6.1 (CH2).
3
2
2
2
2
General Procedure D; yield: 18 mg (99%); colorless oil.
IR (ATR, neat): 3675, 3225, 2987, 2901, 1738 (C=O stretch lactam),
+
ESI-MS: m/z [M + H] calcd for C10H21N O : 229.2; found (%): 229.1
4
2
1
1
1
659, 1620, 1533, 1477, 1461, 1386, 1353, 1293, 1169, 1130, 1078,
+
(100, [M + H] ).
066, 1048, 944, 880, 835, 798, 719, 705, 595, 568, 518, 453, 429 cm–1
.
+
HRMS: m/z [M + H] calcd for C10H21N O : 229.1659; found: 229.1658.
4
2
H NMR (400 MHz, DMSO-d ): δ = 9.05 (br, 1 H, NH), 8.69 (br, 1 H,
6
NH), 3.79 (t, J = 7.2, 2 H, NCH ), 3.43–3.29 (m, 2 H, CH N), 2.63 (t,
2
2
N-(2-Fluoroethyl)-2-oxoazetidine-1-carboximidamide (7h)
General Procedure D; yield: 13 mg (88%); white waxy solid.
IR (ATR, neat): 3238, 3099, 2909, 1732 (C=O stretch lactam), 1667,
J = 8.1 Hz, 2 H, CH ), 2.14–1.98 (m, 2 H, CH ), 1.15 (t, J = 7.1 Hz, 3 H,
2
2
CH3).
13
C NMR (100 MHz, DMSO-d ): δ = 178.9 (C=O), 152.8 (CN ), 47.4
6
3
1
1
4
526, 1471, 1432, 1386, 1370, 1354, 1332, 1284, 1242, 1196, 1175,
(NCH ), 36.9 (CH N), 32.7 (CH ), 17.1 (CH ), 14.0 (CH ).
2 2 2 2 3
134, 1123, 1082, 1043, 854, 840, 796, 723, 613, 559, 526, 488, 464,
+
ESI-MS: m/z [M + H] calcd for C H N O: 156.1; found (%): 156.1
7
14
3
–1
17 cm
.
+
(100, [M + H] ).
+
HRMS: m/z [M + H] calcd for C H N O: 156.1131; found: 156.1127.
7
14
3
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, 3067–3078