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Hydrochloric Acid → 3-{1'-[(1-cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-4-oxospiro[chroman-2,4'-piperidin]-6-yl}benzoic acid

HRID 420122
ノート
印刷プレビュー

反応式

HRID 420122 の反応式
C(N(CC)CC)C.[CH:8]1([N:11]2[C:19]3[C:14](=[C:15]([O:23][CH3:24])[CH:16]=[C:17]([C:20]([OH:22])=O)[CH:18]=3)[CH:13]=[CH:12]2)[CH2:10][CH2:9]1.Cl.[O:26]=[C:27]1[C:41]2[C:36](=[CH:37][CH:38]=[C:39]([C:42]3[CH:43]=[C:44]([CH:48]=[CH:49][CH:50]=3)[C:45]([OH:47])=[O:46])[CH:40]=2)[O:35][C:29]2([CH2:34][CH2:33][NH:32][CH2:31][CH2:30]2)[CH2:28]1.Cl>CN(C=O)C.O>[CH:8]1([N:11]2[C:19]3[C:14](=[C:15]([O:23][CH3:24])[CH:16]=[C:17]([C:20]([N:32]4[CH2:33][CH2:34][C:29]5([CH2:28][C:27](=[O:26])[C:41]6[C:36](=[CH:37][CH:38]=[C:39]([C:42]7[CH:43]=[C:44]([CH:48]=[CH:49][CH:50]=7)[C:45]([OH:47])=[O:46])[CH:40]=6)[O:35]5)[CH2:30][CH2:31]4)=[O:22])[CH:18]=3)[CH:13]=[CH:12]2)[CH2:9][CH2:10]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 666494031-cyclopropyl-4-methoxy-1H-indole-6-carboxylic acidHCID 666495243-(4-Oxo-spiro[chroman-2,4'-piperidin]-6-yl)benzoic acid hydrochloride

生成物 1

HCID 249632573-{1'-[(1-cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-4-oxospiro[chroman-2,4'-piperidin]-6-yl}benzoic acid

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
70 °C

実験手順

N,N′-carbonyldiimidazole (130 mg) and triethylamine (0.446 mL) were added to a solution of 1-cyclopropyl-4-methoxy-1H-indole-6-carboxylic acid (185 mg) in DMF (4 mL), and stirred at 70° C. for 7 hours. To the reaction mixture was added 3-(4-oxo-spiro[chroman-2,4′-piperidin]-6-yl)benzoic acid hydrochloride (374 mg), which was further stirred at that temperature for 16 hours. 1 N hydrochloric acid and water were added to the reaction mixture, and the formed solid was collected by filtration. The resulting solid was recrystallized from methanol, and purified through silica gel column chromatography (chloroform/methanol) to obtain 3-{1′-[(1-cyclopropyl-4-methoxy-1H-indol-6-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}benzoic acid. This was suspended in water (5 mL), and aqueous 1 N sodium hydroxide solution (0.762 mL) was added thereto and stirred at room temperature for 30 minutes. The solution was purified through ODS reversed-phase column chromatography (water/methanol) to obtain the intended compound. 1H-NMR (400 MHz, DMSO-d6) δ: 8.11-8.09 (1H, m), 7.96-7.93 (1H, m), 7.90 (1H, dd, J=8.5, 2.4 Hz), 7.83-7.79 (1H, m), 7.56-7.50 (1H, m), 7.32 (1H, dd, J=7.6, 7.6 Hz), 7.29 (1H, d, J=3.2 Hz), 7.23 (1H, s), 7.20 (1H, d, J=8.5 Hz), 6.59 (1H, s), 6.41-6.39 (1H, m), 4.45-4.11 (1H, br m), 3.86 (3H, s), 3.86-3.55 (1H, br m), 3.52-3.22 (3H, m), 2.93 (2H, s), 2.17-1.64 (4H, br m), 1.11-1.00 (2H, m), 0.96-0.88 (2H, m); MS [M+Na]+=573.

後処理

  1. stirringwas further stirred at that temperature for 16 hours
  2. filtrationthe formed solid was collected by filtration
  3. customThe resulting solid was recrystallized from methanol
  4. custompurified through silica gel column chromatography (chloroform/methanol)

出典と根拠

ORDレコード
ord-5cb339a950b842fabd0cf1e9d3970188
出典データセット
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08093389B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート