1
ꢀAminopyrrolo[2,3ꢀb]pyridines
Russ.Chem.Bull., Int.Ed., Vol. 56, No. 8, August, 2007
1615
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05—106 °C, R = 0.24 (EA). Found (%): C, 67.52; H, 7.97;
dissolved in 5% HCl (30 mL). Neutral impurities were extracted
with ethyl acetate (2×10 mL). The aqueous phase was separated
and alkalified with 12 M NaOH to pH 9. Organic material was
extracted with ethyl acetate (2×10 mL) and the organic extracts
were dried over Na SO and concentrated. Crystallization of the
f
N, 15.59. C H N O. Calculated (%): C, 67.39; H, 7.92;
1
0
14
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N, 15.72. H NMR, δ: 1.45, 1.52 (both s, 3 H each, Me); 5.36 (s,
H, OH); 5.91 (s, 2 H, NH ); 7.18 (t, 1 H, Ph, J = 7.5 Hz); 7.28
1
2
(
t, 2 H, Ph, J = 7.5 Hz); 7.34 (d, 2 H, Ph, J = 7.5 Hz).
MS (M = 178), m/z (Irel (%)): 178 (7); 162 (6); 135 (22); 121
78); 94 (50); 77 (45); 57 (100); 43 (78).
ꢀHydroxyꢀ3ꢀ(3ꢀpyridyl)butanꢀ2ꢀone hydrazone (4b) was
crystallized from toluene. The yield was 1.629 g (91%), m.p.
7 °C, R = 0.17 (EA). Found (%): C, 60.47; H, 7.37; N, 23.33.
2
4
residue from EA—TBME gave colorless needleꢀlike crystals.
The yield of compound 5 was 1.03 g (32%), m.p. 138—139 °C,
(
3
R = 0.55 (EA). Found (%): C, 66.94; H, 6.84; N, 26.22.
f
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C H N . Calculated (%): C, 67.05; H, 6.88; N, 26.07. H NMR,
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3
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δ: 2.18, 2.35 (both s, 3 H each, Me); 5.55 (s, 2 H, NH ); 6.99
f
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C H N O. Calculated (%): C, 60.32; H, 7.31; N, 23.45.
(dd, 1 H, Ar, J = 7.9 Hz, J = 4.3 Hz); 7.77 (d, 1 H, Ar, J =
7.9 Hz); 8.13 (d, 1 H, Ar, J = 4.3 Hz). MS (M = 161),
m/z (Irel (%)): 161 (99%), 146 (35%), 129 (12%), 120 (41%),
105 (100%), 92 (13%), 77 (38%).
9
13
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H NMR, δ: 1.48, 1.55 (both s, 3 H each, Me); 5.60 (s, 1 H,
OH); 5.86 (s, 2 H, NH ); 7.31 (dd, 1 H, Py, J = 8.4 Hz, J =
2
5
5
1
.2 Hz); 7.68 (d, 1 H, Py, J = 8.4 Hz); 8.41 (d, 1 H, Py, J =
.2 Hz); 8.53 (s, 1 H, Py). MS (M = 179), m/z (Irel (%)):
79 (5); 163 (3); 136 (10); 122 (68); 106 (19); 78 (27); 57
B. Tosylhydrazone 4c (0.833 g, 2.5 mmol) was added to PPA
(25 g) preheated to 40 °C. The mixture was thoroughly stirred at
120 °C for 10 min to complete homogenization; the reaction
mixture darkened. On cooling, the product was isolated and
purified as described in procedure A. The conversion of the
(
100); 43 (96).
N´ꢀ[3ꢀHydroxyꢀ3ꢀ(3ꢀpyridyl)butꢀ2ꢀylidene]ꢀ4ꢀmethylbenꢀ
zenesulfonohydrazide (4c). Compound 3b (0.825 g, 5 mmol) and
tosylhydrazine (0.930 g, 5 mmol) were dissolved in toluene
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starting tosylhydrazone into compound 5 was ~60% ( H NMR).
(
25 mL). The mixture was refluxed with a Dean—Stark trap
The yield of purified compound 5 was 0.177 g (44%).
until water evolution ceased. On cooling, the resulting crystals
of compound 4c were filtered off, washed with toluene, and dried.
1ꢀ(2,4ꢀDinitrophenyl)ꢀ3ꢀmethylꢀ4ꢀ(3ꢀpyridyl)pyrazole (6).
Dinitrophenylhydrazone 4d (2.07 g, 6 mmol) was added to PPA
(30 g) preheated to 40 °C. The mixture was thoroughly stirred at
90 °C for 10 min and then at 110 °C for an additional 10 min.
The substrate dissolved incompletely. Complete homogenizaꢀ
tion was attained at 125 °C; at this temperature, the reaction
mixture was stirred for 10 min. On cooling, the mixture was
poured onto ice and neutralized to pH ~7 by adding 12 M NaOH.
The product was extracted with ethyl acetate (3×10 mL). The
combined extracts were dried over Na SO and concentrated to
The yield was 1.582 g (95%), m.p. 207—209 °C, R = 0.64 (EA).
f
Found (%): C, 57.74; H, 5.69; N, 12.55. C H N O S. Calcuꢀ
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19
3
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lated (%): C, 57.64; H, 5.74; N, 12.60. H NMR, δ: 1.46, 1.61,
.42 (all s, 3 H each, Me); 5.88 (s, 1 H, OH); 7.23 (dd, 1 H, Py,
J = 8.2 Hz, J = 4.6 Hz); 7.38 (d, 1 H, Py, J = 8.2 Hz); 7.42, 7.74
both d, 2 H each, Ts, J = 8.0 Hz); 8.30 (s, 1 H, Py) 8.40 (d,
H, Py, J = 4.6 Hz); 10.10 (s, 1 H, NH). MS (M = 332),
m/z (Irel (%)): 333 (1); 212 (12); 178 (20); 139 (28); 122 (100);
06 (38); 91 (72); 78 (23); 65 (40); 57 (95); 43 (91).
ꢀHydroxyꢀ3ꢀ(3ꢀpyridyl)butanꢀ2ꢀone (2,4ꢀdinitropheꢀ
nyl)hydrazone (4d). 2,4ꢀDinitrophenylhydrazine (0.594 g,
mmol) was dissolved under heating in ethanol (6 mL) and
2
(
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2
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a brown oil. The oil was dissolved in hot ethanol. On cooling,
the solution produced yellow crystals. The yield of compound 6
3
was 0.352 g (18%), m.p. 185—186 °C, R = 0.48 (EA). Found (%):
f
3
C, 55.16; H, 3.42; N, 21.74. C H N O . Calculated (%):
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5
11
5
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added to a solution of compound 3b (0.495 g, 3 mmol) in ethaꢀ
nol (4 mL). The mixture was refluxed for 10 min and cooled
to 0 °C. The resulting crystals were filtered off, washed with cold
ethanol, and dried in air. The yield of hydrazone 4d was 1.014 g
C, 55.38; H, 3.41; N, 21.53. H NMR, δ: 2.38 (s, 3 H, Me); 7.50
(dd, 1 H, Py, J = 5.2 Hz, J = 2.9 Hz); 8.00 (d, 1 H, Py, J =
5.2 Hz); 8.17 (d, 1 H, Ph(NO ) , J = 9.4 Hz); 8.55 (d, 1 H, Py,
2
2
J = 2.9 Hz); 8.65 (dd, 1 H, Ph(NO ) , J = 9.4 Hz, J = 2.4 Hz);
2
2
(
98%), m.p. 253—254 °C, R = 0.60 (EA). Found (%): C, 52.30;
8.83 (s, 1 H, Ar); 8.86 (d, 1 H, Ph(NO ) , J = 2.4 Hz); 9.00 (s,
f
2 2
H, 4.37; N, 20.17. C H N O . Calculated (%): C, 52.17;
H, 4.38; N, 20.28. H NMR, δ: 1.80, 1.96 (both s, 3 H each,
Me); 6.32 (s, 1 H, OH); 7.63 (dd, 1 H, Py, J = 8.4 Hz, J =
1 H, Ar). MS (M = 325), m/z (Irel (%)): 325 (100); 295 (40);
249 (46); 208 (21); 159 (15); 131 (19); 117 (24); 91 (21); 64
(23); 43 (28).
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5
15
5
5
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.7 Hz); 7.92 (d, 1 H, Ph(NO ) , J = 9.3 Hz); 8.11 (d, 1 H, Py,
3ꢀHydroxyꢀ3ꢀ(3ꢀpyridyl)butanꢀ2ꢀone oxime (7). Hydroxy
ketone 3b (1.16 g, 7 mmol) and hydroxylamine hydrochloride
(0.49 g, 7 mmol) were dissolved in water (5 mL). A solution of
2
2
J = 8.4 Hz); 8.42 (dd, 1 H, Ph(NO ) , J = 9.3 Hz, J = 2.4 Hz);
8
2
2
.63 (d, 1 H, Py, J = 4.7 Hz); 8.77 (s, 1 H, Py); 8.88 (d, 1 H,
Ph(NO ) , J = 2.4 Hz); 10.78 (s, 1 H, NH). MS (M = 344),
Na CO3 (0.42 g, 4 mmol) in water (4 mL) was added with
2
2
2
m/z (Irel (%)): 327 (2); 310 (9); 280 (19); 239 (22); 192 (10); 166
10); 130 (32); 117 (50); 104 (69); 90 (21); 77 (89); 63 (60);
1 (100).
ꢀAminoꢀ2,3ꢀdimethylꢀ1Hꢀpyrrolo[2,3ꢀb]pyridine
stirring for 15 min. The reaction mixture was stirred for 30 min
and the precipitate that formed was filtered off, washed with
water, and dried in vacuo at 60 °C. The yield of oxime 7 was
(
5
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(5).
1.26 g (100%), m.p. 155 °C, R = 0.45 (EA). Found (%): C, 60.07;
f
A. Hydrazone 4b (20 mmol, 3.58 g) was dissolved under heating
in chloroform (3 mL). Polyphosphoric acid (15 g) was added
and the mixture was gradually (in order to avoid strong foaming)
concentrated in a rotary evaporator at 60 °C. Then the mixture
was heated with stirring to 110 °C and kept for 10 min. On
cooling, the mixture was poured onto ice and alkalified to pH ~9
by adding 12 M NaOH. Organic material was extracted with
ethyl acetate (3×10 mL). The combined extracts were dried over
Na SO and concentrated to an oily brown residue (4.8 g; the
H, 6.77; N, 15.36. C H N O . Calculated (%): C, 59.98;
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12
2
2
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H, 6.71; N, 15.55. H NMR, δ: 1.59, 1.61 (both s, 3 H each,
Me); 5.81 (s, 1 H, C—OH); 7.34 (dd, 1 H, Py, J = 8.1 Hz, J =
4.6 Hz); 7.71 (d, 1 H, Py, J = 8.1 Hz); 8.42 (d, 1 H, Py, J =
4.6 Hz); 8.58 (s, 1 H, Py); 10.75 (s, 1H, N—OH). MS (M = 180),
m/z (Irel (%)): 180 (1); 163 (2); 123 (68); 106 (10); 78 (19); 51
(23); 43 (100).
3ꢀAcetylpyridine (8) and its oxime (9). Oxime 7 (0.72 g,
4 mmol) was added to PPA (20 g) preheated to 40 °C. The
reaction mixture was thoroughly stirred at 100 °C for 10 min to
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content of compound 5 was ~70% ( H NMR)). The residue was