E
Synthesis
R. Bucci et al.
Paper
13
Methyl 5-[4-Morpholino-4-(tosylimino)butyl]-4,5-dihydro-1H-
C NMR (75 MHz, CDCl ): = 17.0 (CH ), 21.4 (CH ), 22.9 (CH ), 30.0
3
3
3
2
pyrazole-3-carboxylate (4a)
(CH ), 33.7 (CH ), 44.1 (CH), 44.7 (CH ), 46.6 (CH ), 51.8 (CH ), 66.3
2 2 2 2 3
(
CH ), 66.6 (CH ), 67.9 (CH), 126.2 (CH), 129.2 (CH), 140.9 (C), 142.2
2 2
Yield (method A): 0.28 g, 65%; yield (method B): 0.32 g, 73%; white
(C), 144.3 (C), 163.3 (C), 166.9 (C).
solid; mp 73 °C (Et O).
2
ESI-MS: m/z = 450.0 [M + H]–.
1
H NMR (300 MHz, CDCl ): = 1.65–1.83 (m, 4 H), 2.42 (s, 3 H), 2.57–
3
2.62 (m, 1 H), 2.72–2.83 (m, 1 H), 2.99–3.19 (m, 2 H), 3.51–3.72 (m, 8
Anal. Calcd for C21H30N O S: C, 55.98; H, 6.71; N, 12.44. Found: C,
4
5
H), 3.84 (s, 3 H), 4.01–4.11 (m, 1 H), 6.68 (very br s, 1 H), 7.27 (d, J =
55.79; H, 6.89; N, 12.31.
8.2 Hz, 2 H), 7.81 (d, J = 8.2 Hz, 2 H).
13
C NMR (75 MHz, CDCl ): = 21.4 (CH ), 23.3 (CH ), 29.9 (CH ), 34.5
Dimethyl 5-[4-Morpholino-4-(tosylimino)butyl]-4,5-dihydro-1H-
3
3
2
2
(
(
(
CH ), 36.4 (CH ), 44.8 (CH ), 46.6 (CH ), 52.0 (CH ), 60.7 (CH), 66.3
pyrazole-3,4-dicarboxylate (4e)
2
2
2
2
3
CH ), 66.6 (CH ), 126.2 (CH), 129.2 (CH), 140.8 (C), 141.7 (C), 142.3
2
2
Yield (method A): 0.33g, 65%; white solid; mp 68 °C (Et O).
2
C), 163.3 (C), 166.9 (C).
1
H NMR (300 MHz, CDCl ): = 1.65–1.94 (m, 4 H), 2.41 (s, 3 H), 2.75–
3
ESI-MS: m/z = 435.35 [M + H]–.
2.88 (m, 1 H), 3.08–3.20 (m, 1 H), 3.45–3.56 (m, 2 H), 3.62–3.79 (m, 7
Anal. Calcd for C20H28N O S: C, 55.03; H, 6.47; N, 12.83. Found: C,
H), 3.77 (s, 3 H), 3.83 (s, 3 H), 4.22–4.34 (m, 1 H), 7.08 (br s, 1 H), 7.28
4
5
54.98; H, 6.60; N, 12.71.
(d, J =8.1 Hz, 2 H), 7.80 (d, J = 8.1 Hz, 2 H).
13
C NMR (75 MHz, CDCl ): = 21.4 (CH ), 22.8 (CH ), 29.7 (CH ), 34.1
3
3
2
2
N-[4-(3-Cyano-4,5-dihydro-1H-pyrazol-5-yl)-1-morpholino-
(CH ), 44.8 (CH ), 46.7 (CH ), 52.2 (CH ), 52.7 (CH ), 54.8 (CH), 65.7
2 2 2 3 3
butylidene]tosylamide (4b)
(CH), 66.3 (CH ), 66.6 (CH ), 126.1 (CH), 129.2 (CH), 137.9 (C), 140.8
2 2
(
C), 142.3 (C), 162.6 (C), 166.7 (C), 171.0 (C).
Yield (method A): 0.27 g, 68%; white solid; mp 148 °C (Et O).
2
–
+
1
ESI-MS: m/z = 493 [M ], 517 [M + Na].
H NMR (300 MHz, CDCl ): = 1.62–1.89 (m, 4 H), 2.43 (s, 3 H), 2.45–
3
2.62 (m, 1 H), 2.72–2.86 (m, 1 H), 2.96–3.10 (m, 1 H), 3.10–3.22 (m, 1
Anal. Calcd for C22H30N O S: C, 53.43; H, 6.11; N, 11.33. Found: C,
4
7
H), 3.48–3.57 (m, 2 H), 3.62–3.78 (m, 6 H), 4.08–4.22 (m, 1 H), 7.09 (br
53.24; H, 6.24; N, 11.21
s, 1 H), 7.28 (d, J = 8.2 Hz, 2 H), 7.79 (d, J = 8.2 Hz, 2 H).
1
3
C NMR (75 MHz, CDCl ) = 21.4 (CH ), 23.7 (CH ), 29.7 (CH ), 34.0
4-Methyl-N-{1-morpholino-4-[(3S,3aS,6aR)-6-oxo-3a,4,6,6a-tetra-
hydro-3H-furo[3,4-c]pyrazol-3-yl]butylidene}benzenesulfon-
amide (4f)
3
3
2
2
(CH ), 38.7 (CH ), 44.8 (CH ), 46.7 (CH ), 60.1 (CH), 66.3 (CH ), 66.6
2 2 2 2 2
(CH ), 115.1 (C), 122.4 (C), 126.4 (CH), 129.2 (CH), 140.7 (C), 142.4 (C),
2
1
66.8 (C).
Yield (method A): 0.35 g, 67%; white powder; mp 155–156 °C (Et O).
2
ESI-MS: m/z = 402.4 [M + H]–.
1
H NMR (300 MHz, CDCl ): = 1.84–2.25 (m, 4 H), 2.43 (s, 3 H), 2.72–
3
Anal. Calcd for C19H25N O S: C, 56.56; H, 6.25; N, 17.36. Found: C,
2.94 (m, 1 H), 2.94–3.08 (m, 1 H), 3.18–3.34 (m, 1 H), 3.51–3.85 (m, 8
H), 3.98–4.08 (m, 1 H), 4.60–4.69 (m, 1 H), 4.92–5.02 (m, 1 H), 5.64–
5
3
56.39; H, 6.40; N, 17.20.
5.70 (m, 1 H), 7.28 (d, J = 8.2 Hz, 2 H), 7.81 (d, J = 8.2 Hz, 2 H).
1
3
N-Isopropyl-5-[4-morpholino-4-(tosylimino)butyl]-4,5-dihydro-
H-pyrazole-3-carboxamide (4c)
C NMR (75 MHz, CDCl ): = 21.4 (CH ) 23.6 (CH ), 30.1 (CH ), 32.4
3
3
2
2
1
(CH ), 37.1 (CH), 44.8 (CH ), 46.7 (CH ), 66.3 (CH ), 66.6 (CH ), 72.7
2 2 2 2 2
(
CH ), 92.8 (CH), 98.6 (CH), 126.1 (CH), 129.2 (CH), 140.8 (C), 142.3
Yield (method A): 0.32 g, 65%; white powder; mp 62 °C (Et O).
2
2
(C), 166.6 (C), 168.5 (C).
1
H NMR (300 MHz, CDCl ): = 1.17 (d, J = 6.6 Hz, 6 H), 1.68–1.85 (m, 4
3
+
ESI-MS: m/z = 457.7 [M + Na].
H), 2.41 (s, 3 H), 2.45–2.58 (m, 1 H), 2.76–2.89 (m, 1 H), 3.01- 3.19 (m,
2 H), 3.48–3.57 (m, 2 H), 3.62–3.78 (m, 6 H), 3.92–4.08 (m, 1 H), 4.08–
4.18 (m, 1 H), 6.30–6.65 (2br s, 2 H), 7.28(d, J = 8.1 Hz, 2 H), 7.80 (d, J =
8.1 Hz, 2 H).
Anal. Calcd for C20H26N O S: C, 55.28; H, 6.03; N, 12.89. Found: C,
55.17; H, 6.22; N, 12.77.
4
5
1
3
C NMR (75 MHz, CDCl ): = 21.4 (CH ), 22.7 (CH ), 23.6 (CH ), 29.9
4-Methyl-N-{1-morpholino-4-[(3S,3aS)-7-oxo-2,3,3a,4,5,7-hexahy-
dropyrano[3,4-c]pyrazol-3-yl]butylidene}benzensulfonamide (4g)
3
3
3
2
(
(
(
CH ), 34.5 (CH ), 36.4 (CH ), 41.1 (CH ), 44.8 (CH), 46.6 (CH ), 60.5
CH), 66.3 (CH ), 66.6 (CH ), 126.2 (CH), 129.2 (CH), 140.9 (C), 142.2
C), 147.5 (C), 161.5 (C), 167.0 (C).
2 2 2 2 2
2
2
Yield (method A): 0.27g, 62%; glassy solid.
1
H NMR (300 MHz, CDCl ): = 1.74–2.20 (m, 6 H), 2.41 (s, 3 H), 2.77–
3
ESI-MS: m/z = 487.8 [M + Na]+.
2.87 (m, 1 H), 2.96–3.06 (m 1 H), 3.12–3.22 (m, 1 H), 3.53–3.72 (m, 8
Anal. Calcd for C22H33N O S C, 57.00; H, 7.17; N, 15.11. Found: C,
H), 3.91–4.03 (m, 1 H), 4.33–4.41 (m, 1 H), 4.43–4.55 (m, 1 H), 7.27 (d,
5
4
56.92; H, 7.32; N, 14.98
J = 8.2 Hz, 2 H), 7.29 (br s, 1 H), 7.79 (d, J = 8.2 Hz, 2 H).
13
C NMR (75 MHz, CDCl ): = 21.5 (CH ), 23.9 (CH ), 27.9 (CH ), 30.0
3
3
2
2
Methyl (4R,5R)-4-Methyl-5-[4-morpholino-4-(tosylimino)butyl]-
,5-dihydro-1H-pyrazol-3-carboxylate (4d)
(CH ), 33.0 (CH ), 44.8 (CH ), 46.7 (CH ), 47.2 (CH), 66.3 (CH ), 66.6
(CH ), 69.1 (CH ), 69.9 (CH),126.1 (CH), 129.2 (CH), 140.7 (C), 142.0
2 2
2 2 2 2 2
4
(
C), 142.3 (C), 160.1 (C), 166.9 (C).
Yield (method A): 0.30 g, 68%; white powder; mp 143 °C (Et O).
2
–
+
1
ESI-MS: m/z = 448.7 [M ], 471.12 [M + Na].
H NMR (300 MHz, CDCl ): = 1.27 (d, J =7.8 Hz, 3 H), 1.59–1.90 (m, 4
3
H), 2.41 (s, 3 H), 2.52–2.57 (m, 1 H), 2.57–2.95 (m, 1 H), 3.10–3.25 (m,
Anal. Calcd for C21H28N O S: C, 56.23; H, 6.29; N, 12.48. Found: C,
4
5
1
H), 3.48–3.55 (m, 2 H), 3.55–3.62 (m, 1 H), 3.62–3.80 (m, 6 H), 3.83
56.08; H, 6.33; N, 12.34.
(s, 3 H), 6.75 (br s, 1 H), 7.27(d, J = 8.1 Hz, 2 H), 7.80 (d, J =8.1 Hz, 2 H).
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2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G