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Potassium Carbonate → (+/-)-2-(trans-2-Hydroxycyclohexyl)-5-[(6'-methyl-2,3'-bipyridin-5-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one

HRID 2067111
ノート
印刷プレビュー

反応式

HRID 2067111 の反応式
C[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][C:3]=1[CH2:14][N:15]1[C:20]2[N:21]=[CH:22][CH:23]=[CH:24][C:19]=2[C:18](=S)[C:17]([C:26](OCC)=[O:27])=[N:16]1.[NH:31]([C@@H:33]1[CH2:38][CH2:37][CH2:36][CH2:35][C@H:34]1[OH:39])[NH2:32].[C:40](=O)([O-])[O-].[K+].[K+].C(=O)(O)[O-].[Na+]>C(O)C.[Hg](Cl)Cl>[OH:39][C@@H:34]1[CH2:35][CH2:36][CH2:37][CH2:38][C@H:33]1[N:31]1[C:26](=[O:27])[C:17]2=[N:16][N:15]([CH2:14][C:3]3[CH:4]=[CH:5][C:6]([C:8]4[CH:9]=[N:10][C:11]([CH3:40])=[CH:12][CH:13]=4)=[N:7][CH:2]=3)[C:20]3[N:21]=[CH:22][CH:23]=[CH:24][C:19]=3[C:18]2=[N:32]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 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 13403698trans-2-HydrazinocyclohexanolHCID 86662100Ethyl 1-[(6-methyl-2,3'-bipyridin-5-yl)methyl]-4-thioxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate

生成物 1

HCID 49763347(+/-)-2-(trans-2-Hydroxycyclohexyl)-5-[(6'-methyl-2,3'-bipyridin-5-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]pyrido[3,2-e]pyridazin-3-one

試薬・触媒・溶媒 2

HCID 24085Mercuric Chloride触媒HCID 702Ethanol溶媒

反応条件

温度
70 °C

実験手順

Ethyl 1-[(6-methyl-2,3′-bipyridin-5-yl)methyl]-4-thioxo-1,4-dihydropyrido[2,3-c]pyridazine-3-carboxylate [(Example 6, Step 2), 47 mg, 0.11 mmol], (±)-trans-2-hydrazinocyclohexanol (44 mg, 0.34 mmol, 3 equiv), potassium carbonate (0.16 g, 1.1 mmol, 10 equiv) and mercury(II) chloride (31 mg, 0.11 mmol, 1 equiv) were combined in ethanol (10 mL) at ambient temperature and after 5 minutes, the mixture was warmed to 70° C. for 3 h. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (100 mL, aqueous saturated) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by preparative TLC (eluting with ethyl acetate containing 10% methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 9.02 (1H, d, J=2.1 Hz), 8.93 (1H, d, J=2.0 Hz), 8.75 (1H, dd, J=4.6, 1.8 Hz), 8.52 (1H, dd, J=8.1, 1.8 Hz), 8.16 (1H, dd, J=8.2, 2.4 Hz), 7.97 (1H, dd, J=8.3, 2.3 Hz), 7.66 (1H, dd, J=8.2, 0.6 Hz), 7.50 (1H, dd, J=8.0, 4.6 Hz), 7.23 (1H, d, J=8.0 Hz), 6.0 (1H, d, J=14.3 Hz), 5.96 (1H, d, J=14.3 Hz), 4.30 (1H, ddd, J=11.7, 9.8, 4.1 Hz), 4.07-4.01 (1H, m,), 2.60 (3H, s), 2.20 (1H, br d, J=10.3 Hz), 2.01 (1H, br d, J=11.9 Hz), 1.89-1.79 (2H, m), 1.72-1.53 (2H, m), 1.50-1.39 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 468.2142 [(M+H)+; calculated for C26H26N7O2: 468.2143].

後処理

  1. temperatureThe mixture was cooled to ambient temperature
  2. extractionextracted with ethyl acetate (3×75 mL)
  3. dry with materialThe combined organic extracts were dried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by preparative TLC (eluting with ethyl acetate containing 10% methanol)

出典と根拠

ORDレコード
ord-aacd68996f694bbf9f071495728de00a
出典データセット
uspto-grants-2012_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08293744B2

反応ノート

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