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127.3, 119.4, 117.1, 117.0, 114.2, 112.8, 105.3, 102.0, 56.2, 55.5 ppm;
(ESI): m/z 327 [M+H]+; Anal. calcd for C18H18N2O4: C 66.25, H 5.56,
N 8.58, found: C 66.39, H 5.55, N 8.66.
IR (KBr): n˜ =3359, 2834, 1623, 1511, 1283, 1226, 1198, 1071 cmÀ1
;
MS (ESI): m/z 313 [M+H]+; Anal. calcd for C17H16N2O4: C 65.38, H
6-(4-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-3-yl)-2,3-
dimethoxyphenol (18): Purification by column chromatography
(PE/EtOAc, 6:4) gave 18 as a white solid (97 mg, 55%): mp: 176–
5.16, N 8.97, found: C 65.41, H 5.12, N 9.05.
5-Methoxy-2-(4-(4-methoxyphenyl)-1H-pyrazol-3-yl)phenol (12):
Purification by column chromatography (PE/EtOAc, 7:3) gave 13 as
a white solid (95 mg, 64%): mp: 204–2058C (ref. [15a] 150.5–
151.68C); MS (ESI): m/z 297 [M+H]+; Anal. calcd for C17H16N2O3: C
68.91, H 5.44, N 9.45, found: C 68.99, H 5.60, N 9.46.
1
1778C; H NMR (300 MHz, CDCl3, 258C): d=9.72 (brs, 1H), 7.57 (s,
1H), 7.01 (d, J=8.8 Hz, 1H), 6.87–6.81 (m, 3H), 6.32 (d, J=8.8 Hz,
1H), 4.27 (s, 4H), 3.92 (s, 3H), 3.83 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3, 258C): d=152.7, 149.0, 143.5, 142.8, 136.5, 126.9 (2C), 123.7,
122.6, 119.5, 118.0, 117.4 (2C), 110.9, 103.4, 64.5, 64.4, 60.9,
55.9 ppm; IR (KBr): n˜ =3404, 2931, 1522, 1468, 1431, 1297, 1280,
1084 cmÀ1; MS (ESI): m/z 355 [M+H]+; Anal. calcd for C19H18N2O5: C
64.40, H 5.12, N 7.91, found: C 64.56, H 5.22, N 7.98.
2-(4-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-3-yl)-5-me-
thoxyphenol (13):[18] Purification by column chromatography (PE/
EtOAc, 8:2) gave 13 as a white solid (86 mg, 53%): mp: 122–
1
1238C; H NMR (300 MHz, CDCl3, 258C): d=10.38 (brs, 1H), 7.54 (s,
6-(4-(Benzo[d][1,3]dioxol-5-yl)-1H-pyrazol-3-yl)-2,3-dimethoxy-
phenol (19): Purification by column chromatography (PE/EtOAc,
7:3) gave 19 as a white solid (107 mg, 63%): mp: 174–1758C;
1H NMR (300 MHz, CDCl3, 258C): d=10.12 (brs, 1H), 7.57 (s, 1H),
6.97 (d, J=9.0 Hz, 1H), 6.83–6.80 (m, 3H), 6.33 (d, J=9.0 Hz, 1H),
5.97 (s, 2H), 3.92 (s, 3H), 3.83 ppm (s, 3H); 13C NMR (75 MHz, CDCl3,
258C): d=152.8, 149.1, 147.8, 146.8, 136.6, 132.2, 132.1, 128.8,
127.4, 123.6, 122.7, 110.9, 109.9, 108.5, 103.3, 101.1, 60.9, 55.9 ppm;
IR (KBr): n˜ =3386, 2953, 1607, 1465, 1435, 1233, 1080 cmÀ1; MS
(ESI): m/z 341 [M+H]+; Anal. calcd for C18H16N2O5: C 63.52, H 4.74,
N 8.23, found: C 63.48, H 4.65, N 8.12.
1H), 7.19 (d, J=8.8 Hz, 1H), 6.87–6.79 (m, 3H), 6.57 (s, 1H), 6.27 (d,
J=8.8 Hz, 1H), 4.28 (s, 4H), 3.77 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3, 258C): d=160.5, 157.3, 147.0, 143.6, 143.0, 129.4, 129.2,
126.4, 122.8, 119.7, 118.3, 117.5, 110.0, 105.8, 101.8, 64.5 (2C),
55.3 ppm; IR (KBr): n˜ =3296, 2975, 1628, 1582, 1502, 1282,
1069 cmÀ1; MS (ESI): m/z 325 [M+H]+; Anal. calcd for C18H16N2O4: C
66.66, H 4.97, N 8.64, found: C 66.73, H 5.01, N 8.61.
2-(4-(Benzo[d][1,3]dioxol-5-yl)-1H-pyrazol-3-yl)-5-methoxyphenol
(14): Purification by column chromatography (PE/EtOAc, 8:2) gave
14 as a white solid (74 mg, 48%): mp: 161–1628C; 1H NMR
(300 MHz, CDCl3, 258C): d=10.37 (brs, 1H), 7.54 (s, 1H), 7.15 (d,
J=8.5 Hz, 1H), 6.84–6.80 (m, 3H), 6.57 (d, J=1.6 Hz, 1H), 6.28 (dd,
J=8.5/1.6 Hz, 1H), 5.99 (s, 2H), 3.77 ppm (s, 3H); 13C NMR (75 MHz,
CDCl3, 258C): d=160.6, 157.4, 147.9, 146.5, 146.4, 129.4, 129.1,
126.8, 123.0, 119.9, 110,1, 109.9, 108.6, 105.8, 101.8, 101.2,
55.3 ppm; IR (KBr): n˜ =3275, 1627, 1585, 1439, 1242, 1198,
1042 cmÀ1; MS (ESI): m/z 311 [M+H]+; Anal. calcd for C17H14N2O4: C
65.80, H 4.55, N 9.03, found: C 65.94, H 4.61, N 9.09.
2,3,4-Trimethoxy-6-(4-(3,4,5-trimethoxyphenyl)-1H-pyrazol-3-yl)-
phenol (20): Purification by column chromatography (PE/EtOAc,
7:3) gave 20 as an amorphous solid (93 mg, 45%): 1H NMR
(300 MHz, CDCl3, 258C): d=7.64 (s, 1H), 6.61 (s, 1H), 6.60 (s, 2H),
3.96 (s, 3H), 3.89 (s, 3H), 3.85 (s, 3H), 3.80 (s, 6H), 3.38 ppm (s, 3H);
13C NMR (75 MHz, CDCl3, 258C): d=153.3, 145.7, 143.5, 142.6, 141.7,
137.2, 129.4, 120.0, 118.5, 111.0, 106.9 (2C), 106.5, 61.3, 61.2, 61.0,
56.3, 55.7 ppm; IR (KBr): n˜ =3300, 2937, 2833, 1583, 1463, 1238,
1126 cmÀ1; MS (ESI): m/z 417 [M+H]+; Anal. calcd for C21H24N2O7: C
60.57, H 5.81, N 6.73, found: C 60.76, H 5.90, N 6.85.
2,3-Dimethoxy-6-(4-(3,4,5-trimethoxyphenyl)-1H-pyrazol-3-yl)-
phenol (15): Purification by column chromatography (PE/EtOAc,
8:2) gave 15 as a white solid (129 mg, 67%): mp: 170–1718C;
1H NMR (300 MHz, CDCl3, 258C): d=9.24 (brs, 1H), 7.64 (s, 1H),
7.02 (d, J=8.8 Hz, 1H), 6.58 (s, 2H), 6.32 (d, J=8.8 Hz, 1H), 3.92 (s,
3H), 3.89 (s, 3H), 3.80 (s, 3H), 3.77 (s, 6H) 3.77 ppm (s, 3H);
13C NMR (75 MHz, CDCl3, 258C): d=153.8, 153.2, 150.5, 149.8, 136.9,
136.1, 130.6, 130.2, 129.9, 120.0, 119.7, 104.7, 103.7, 60.7, 60.6, 56.3,
56.0 ppm; IR (KBr): n˜ =3416, 3053, 2940, 1580, 1431, 1121,
1091 cmÀ1; MS (ESI): m/z 387 [M+H]+; Anal. calcd for C20H22N2O6: C
62.17, H 5.74, N 7.25, found: C 62.19, H 5.75, N 7.20.
6-(4-(3-Hydroxy-4-methoxyphenyl)-1H-pyrazol-3-yl)-2,3,4-trime-
thoxyphenol (21): Purification by column chromatography (PE/
EtOAc, 7:3) gave 21 as a white solid (128 mg, 69%); mp: 224–
1
2258C; H NMR (300 MHz, CDCl3, 258C): d=10.77 (brs, 1H), 7.42 (s,
1H), 6.83 (d, J=1.4 Hz, 1H), 6.78–6.71 (m, 2H), 6.58 (s, 1H), 3.83 (s,
3H), 3.77 (s, 6H), 3.27 ppm (s, 3H); 13C NMR (75 MHz, CDCl3, 258C):
d=146.7, 146.3, 144.9, 143.5, 142.3, 141.8, 126.9, 126.6, 120.9,
119.4, 116.8, 112.3, 112.0, 111.4, 106.4, 61.0, 60.8, 56.0, 55.6 ppm; IR
(KBr): n˜ =3398, 3276, 2934, 1560, 1507, 1463, 1429, 1255,
1071 cmÀ1; MS (ESI): m/z 373 [M+H]+; Anal. calcd for C19H20N2O6: C
61.28, H 5.41, N 7.52, found: C 61.33, H 5.50, N 7.59.
6-(4-(3-Hydroxy-4-methoxyphenyl)-1H-pyrazol-3-yl)-2,3-dime-
thoxyphenol (16): Purification by column chromatography (PE/
EtOAc, 6:4) gave 16 as a white solid (68 mg, 40%): mp: 185–
1868C; 1H NMR (300 MHz, [D6]DMSO, 258C): d=8.84 (s, 1H), 7.58
(brs, 1H), 6.85–6.80 (m, 2H), 6.70–6.65 (m, 2H), 6.48 (d, J=7.1 Hz,
1H), 3.77 (s, 3H), 3.73 (s, 3H), 3.69 ppm (s, 3H); IR (KBr): n˜ =3408,
3050, 2955, 1581, 1420, 1127, 1090 cmÀ1; MS (ESI): m/z 343 [M+H]+
; Anal. calcd for C18H18N2O5: C 63.15, H 5.30, N 8.18, found: C 63.11,
H 5.29, N 8.09.
2,3,4-Trimethoxy-6-(4-(4-methoxyphenyl)-1H-pyrazol-3-yl)phenol
(22): Purification by column chromatography (PE/EtOAc, 7:3) gave
22 as a white solid (94 mg, 53%): mp: 158–1598C; 1H NMR
(300 MHz, CDCl3, 258C): d=7.59 (s, 1H), 7.30 (d, J=8.8 Hz, 2H),
6.93 (d, J=8.8 Hz, 2H), 6.59 (s, 1H), 3.98 (s, 3H), 3.90 (s, 3H), 3.82
(s, 3H), 3.35 ppm (s, 3H); 13C NMR (75 MHz, CDCl3, 258C): d=159.0,
145.6, 143.2, 142.5, 141.7, 131.0, 130.5, 125.9, 119.8, 114.0, 111.2,
106.5, 105.1, 61.2 (2C), 55.7, 55.5 ppm; IR (KBr): n˜ =3390, 2935,
2359, 1556, 1461, 1417, 1248, 1084 cmÀ1; MS (ESI): m/z 357
[M+H]+; Anal. calcd for C19H20N2O5: C 64.04, H 5.66, N 7.86, found:
C 63.99, H 5.65, N 7.87.
2,3-Dimethoxy-6-(4-(4-methoxyphenyl)-1H-pyrazol-3-yl)phenol
(17): Purification by column chromatography (PE/EtOAc, 7:3) gave
17 as a white solid (102 mg, 63%): mp: 193–1948C; 1H NMR
(300 MHz, CDCl3, 258C): d=7.59 (s, 1H), 7.26 (d, J=6.6 Hz, 2H),
6.94 (d, J=6.6 Hz, 2H), 6.91 (d, J=8.8 Hz, 1H), 6.30 ppm (d, J=
8.8 Hz, 1H); 13C NMR (75 MHz, CDCl3, 258C): d=158.8, 152.7, 149.1,
136.6, 130.5, 125.9, 123.6, 119.6, 114.1, 111.0, 103.3, 60.9, 55.9,
55.3 ppm; IR (KBr): n˜ =3406, 2559, 1523, 1466, 1293, 1081 cmÀ1; MS
General procedure for the synthesis of intermediates 25a–c: A
mixture of 3-methoxycatechol 23 (800 mg, 1.5 equiv), phenylacetic
acid 24 (24a 858 mg, 24b 692 mg, 24c 632 mg, 1 equiv), p-TsOH
(36 mg, 0.05 equiv), and BF3·Et2O (1 mL per mmol of 23) was
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ChemMedChem 2013, 8, 633 – 643 640