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1,4-Dioxane → 3-Methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol

HRID 1027225
ノート
印刷プレビュー

反応式

HRID 1027225 の反応式
O1CCOCC1.C([Si]([O:14][C:15]1[CH:20]=[CH:19][C:18](B2OC(C)(C)C(C)(C)O2)=[C:17]([O:30][CH3:31])[CH:16]=1)(C)C)(C)(C)C.Cl[C:33]1[N:38]=[N:37][C:36]([N:39]([CH3:50])[CH:40]2[CH2:45][C:44]([CH3:47])([CH3:46])[NH:43][C:42]([CH3:49])([CH3:48])[CH2:41]2)=[CH:35][CH:34]=1.C(=O)(O)[O-].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[CH3:31][O:30][C:17]1[CH:16]=[C:15]([OH:14])[CH:20]=[CH:19][C:18]=1[C:33]1[N:38]=[N:37][C:36]([N:39]([CH3:50])[CH:40]2[CH2:45][C:44]([CH3:46])([CH3:47])[NH:43][C:42]([CH3:49])([CH3:48])[CH2:41]2)=[CH:35][CH:34]=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 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 867105396-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2 回HCID 86710628Tert-butyl(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)dimethylsilane

生成物 1

HCID 1363771523-Methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol
収率 53%

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒

反応条件

温度
72 °C

実験手順

A 20 L jacketed reactor fitted with a reflux condenser, N2 inlet, thermocouple and overhead stirrer was charged with 2.7 L of dioxane followed by tert-butyl(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)dimethylsilane (290 g, 557 mmol), 6-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (Intermediate 1-1, 113 g, 398 mmol), and sodium bicarbonate (100 g, 1194 mmol). 700 mL of water was added, followed by addition of Pd(PPh3)4 (27.6 g, 23.88 mmol). The reaction mixture was heated at 72° C. overnight. After cooling to RT, the layers were separated. The organic layer was concentrated, and the reside was purified by silica gel chromatography using 5% MeOH (containing 1% TEA) in DCM to provide the desired product, 3-methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenol (83 g, 211 mmol, 53% yield). MS=371.4.

後処理

  1. customfitted with a reflux condenser, N2 inlet
  2. temperatureAfter cooling to RT
  3. customthe layers were separated
  4. concentrationThe organic layer was concentrated
  5. customthe reside was purified by silica gel chromatography

出典と根拠

ORDレコード
ord-959fae3c1a954c4ea14a48938bb53af9
出典データセット
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08729263B2

反応ノート

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