N
Synthesis
E. Diamanti et al.
Feature
1
13
H NMR (101 MHz, CDCl ): δ = 11.39 (s, 1 H), 8.85–9.42 (m, 1 H), 5.15
C NMR (101 MHz, CDCl ): δ = 152.0, 150.0, 129.3, 108.6, 40.4, 31.6,
3
3
(s, 1 H), 3.22–3.39 (m, 2 H), 2.21 (s, 3 H), 1.48–1.66 (m, 2 H), 1.18–
29.8, 26.6, 22.7, 14.1, 13.8.
1
.38 (m, 6 H), 0.75–0.90 (m, 3 H).
+
+
–
MS (ESI): m/z = 210 [M + H] , 232 [M + Na] , 208 [M – H] .
13
C NMR (101 MHz, CDCl ): δ = 164.2, 150.0, 149.9, 92.6, 39.9, 31.4,
3
2
9.6, 26.6, 12.2, 22.5, 14.0.
2
4d
+
+
MS (ESI): m/z = 226 [M + H] , 248 [M + Na] .
MS (ESI): m/z = 224 [M – H]–.
Yield: 0.02 g (14%); colorless oil.
1
H NMR (400 MHz, CDCl ): δ = 7.41 (d, J = 1.5 Hz, 1 H), 7.32 (m, 1 H),
3
6.08 (m, 1 H), 3.36 (td, J = 6.0, 7.2 Hz, 2 H), 2.60 (s, 3 H), 1.53–1.70 (m,
N-Hexyl-3-hydroxypyrazole-1-carboxamide (23c) and N-Hexyl-5-
2 H), 1.24–1.43 (m, 6 H), 0.87 (t, J = 7.0 Hz, 3 H).
hydroxypyrazole-1-carboxamide (24c)
13
C NMR (101 MHz, CDCl ): δ = 151.4, 143.0, 140.4, 109.2, 40.3, 31.6,
3
The reaction was carried out following the general procedure de-
29.7, 26.7, 22.7, 14.2, 14.1.
scribed above, dissolving 14c (0.30 g, 3.56 mmol) in anhyd pyridine
+
+
MS (ESI): m/z = 210 [M + H] , 228 [M + NH ] .
4
(17.8 mL) and employing hexyl isocyanate (0.57 mL, 3.92 mmol). The
MS (ESI): m/z = 208 [M – H]–.
two regioisomers 23c and 24c were obtained in a ratio of 67:33, de-
1
termined by H NMR of the crude. The mixture was separated by
3
-Amino-N-hexylpyrazole-1-carboxamide (23e) and 5-Amino-N-
hexylpyrazole-1-carboxamide (24e)
HPLC-MS.
The reaction was carried out following the general procedure de-
scribed above, dissolving 14e (0.20 g, 2.41 mmol) in anhyd pyridine
2
3c
Yield: 0.19 g (25%); light yellow powder; mp 88 °C.
(12 mL) and employing hexyl isocyanate (0.39 mL, 2.65 mmol). The
1
H NMR (400 MHz, CDCl ): δ = 8.04 (d, J = 2.9 Hz, 1 H), 6.45 (t, J = 5.4
3
two regioisomers 23e and 24e were obtained in a ratio of 14:86, de-
Hz, 1 H), 5.88 (d, J = 2.9 Hz, 1 H), 3.38 (td, J = 5.9, 7.1 Hz, 2 H), 1.52–
1
termined by H NMR of the crude. The mixture was separated by sili-
1.70 (m, 2 H), 1.21–1.48 (m, 6 H), 0.89 (t, J = 6.7 Hz, 3 H).
ca gel column chromatography to afford 23e (cyclohexane/EtOAc,
60:40) and 24e (cyclohexane/EtOAc, 70:30).
13
C NMR (101 MHz, CDCl ): δ = 163.1, 149.7, 131.4, 96.5, 40.7, 31.6,
3
29.6, 26.5, 22.7, 14.1.
+
+
+
MS (ESI): m/z = 212 [M + H] , 234 [M + Na] , 250 [M + K] .
23e
MS (ESI): m/z = 210 [M – H]–.
Yield: 0.05 g (11%); yellow oil.
1
H NMR (400 MHz, CDCl ): δ = 7.95 (d, J = 2.8 Hz, 1 H), 6.67–6.91 (m, 1
3
24c
H), 5.77 (d, J = 2.7 Hz, 1 H), 3.45–3.67 (br s, 2 H), 3.34 (td, J = 5.9, 7.1
Hz, 2 H), 1.51–1.66 (m, 2 H), 1.25–1.39 (m, 6 H), 0.87 (t, J = 6.4 Hz, 3
H).
Yield: 0.11 g (14%); white powder; mp 85 °C.
1
H NMR (101 MHz, CDCl ): δ (major rotamer) = 0.89 (t, J = 6.7 Hz, 3
3
13
C NMR (101 MHz, CDCl ): δ = 156.2, 150.1, 130.2, 98.1, 40.3, 31.6,
H), 1.27–1.44 (m, 6 H), 1.53–1.69 (m, 2 H), 3.38 (q, J = 7.0 Hz, 2 H),
3
29.8, 26.6, 22.6, 14.1.
5.50 (app s, 1 H), 7.34 (app s, 1 H), 9.03 (m, 1 H), 10.38 (s, 1 H); δ (mi-
+
+
nor rotamer) = 0.89 (t, J = 6.7 Hz, 3 H), 1.27–1.44 (m, 6 H), 1.53–1.69
MS (ESI): m/z = 211 [M + H] , 233 [M + Na] .
(
(
1
m, 2 H), 3.38 (q, J = 7.0 Hz, 2 H), 5.44 (app s, 1 H), 7.06 (m, 1 H), 7.48
app s, 1 H) ; 1:0.7 ratio of two rotamers.
2
4e
3
C NMR (101 MHz, CDCl ); two rotamers: δ (major rotamer) =
Yield: 0.25 g (50%); colorless oil.
3
1
56.79, 149.86, 142.30, 88.09, 39.97, 31.53, 29.61, 26.58, 22.66, 14.13;
δ (minor rotamer) = 163.86, 149.88, 137.49, 94.76, 40.10, 31.53,
9.61, 26.58, 22.66, 14.13.
1
H NMR (400 MHz, CDCl ): δ = 7.26 (d, J = 1.1 Hz, 1 H), 7.07–7.23 (m, 1
3
H), 5.46–5.78 (br s, 2 H), 5.38 (d, J = 1.8 Hz, 1 H), 3.35 (td, J = 6.0, 7.1
Hz, 2 H), 1.52–1.68 (m, 2 H), 1.25–1.44 (m, 6 H), 0.89 (t, J = 6.6 Hz, 3
H).
13
2
+
+
+
MS (ESI): m/z = 212 [M + H] , 234 [M + Na] , 250 [M + K] .
MS (ESI): m/z = 210 [M – H]–.
C NMR (101 MHz, CDCl ): δ = 153.0, 149.6, 141.2, 89.0, 40.0, 31.6,
3
29.7, 26.6, 22.7, 14.1.
N-Hexyl-3-methylpyrazole-1-carboxamide (23d) and N-Hexyl-5-
methylpyrazole-1-carboxamide (24d)
+
+
MS (ESI): m/z = 211 [M + H] , 233 [M + Na] .
The reaction was carried out following the general procedure de-
scribed above, dissolving 14d (0.05 mL, 0.61 mmol) in anhyd pyridine
3
-Bromo-N-hexylpyrazole-1-carboxamide (23h) and 5-Bromo-N-
hexylpyrazole-1-carboxamide (24h)
(6.1 mL) and employing hexyl isocyanate (0.13 mL, 0.91 mmol). The
The reaction was carried out following the general procedure de-
scribed above, dissolving 14h (0.15 g, 1.02 mmol) in anhyd pyridine
two regioisomers 23d and 24d were obtained in a ratio of 66:34, de-
1
termined by H NMR of the crude. The mixture was separated by sili-
(5.0 mL) and employing hexyl isocyanate (0.22 mL, 1.53 mmol). The
ca gel column chromatography to afford 23d (cyclohexane/EtOAc,
two regioisomers 23h and 24h were obtained in a ratio of 92:8, deter-
mined by H NMR of the crude. The mixture was separated by silica
92:8) and 24d (cyclohexane/EtOAc, 95:5).
1
gel column chromatography to afford 23h (cyclohexane/EtOAc,
23d
99.5:0.5). Compound 24h was not isolated.
Yield: 0.08 g 65%); colorless oil.
1
H NMR (400 MHz, CDCl ): δ = 8.09 (d, J = 2.6 Hz, 1 H), 7.07 (m, 1 H),
23h
3
6
1
.16 (d, J = 2.6 Hz, 1 H), 3.38 (td, J = 6.0, 7.2 Hz, 2 H), 2.28 (s, 3 H),
.51–1.69 (m, 2 H), 1.24–1.43 (m, 6 H), 0.88 (t, J = 6.0 Hz, 3 H).
Yield: 0.10 g (54%); colorless oil.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–R