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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
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HRID 1027225 반응식
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
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참가 물질

7

반응물 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 867105396-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine2회HCID 86710628Tert-butyl(3-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)dimethylsilane

생성물 1

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

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매

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온도
72 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-959fae3c1a954c4ea14a48938bb53af9
출처 데이터셋
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08729263B2

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