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Dimethylformamide → 2-Fluoro-4-(1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzoic acid

HRID 1878778
ノート
印刷プレビュー

反応式

HRID 1878778 の反応式
Cl[C:2]1[CH:3]=[CH:4][C:5](=[O:23])[N:6]([CH2:8][CH2:9][O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[CH:13][CH:12]=2)[N:7]=1.Br[C:25]1[CH:33]=[CH:32][C:28]([C:29]([OH:31])=[O:30])=[C:27]([F:34])[CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+].CN(C=O)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[F:34][C:27]1[CH:26]=[C:25]([C:2]2[CH:3]=[CH:4][C:5](=[O:23])[N:6]([CH2:8][CH2:9][O:10][C:11]3[C:20]4[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=4)[N:14]=[CH:13][CH:12]=3)[N:7]=2)[CH:33]=[CH:32][C:28]=1[C:29]([OH:31])=[O:30]
参加物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 6228DimethylformamideHCID 10340Sodium CarbonateHCID 3026814-Bromo-2-fluorobenzoic acidHCID 598430126-chloro-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one

生成物 1

HCID 598430892-Fluoro-4-(1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzoic acid収率 65.1%

試薬・触媒・溶媒 2

HCID 178418476HCID 178418476、化合物触媒
HCID 962Water溶媒

実験手順

To a 5 ml CEM microwave tube was added 6-chloro-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one (0.1 g, 0.3 mmol), 4-bromo-2-fluorobenzoic acid (0.08 g, 0.5 mmol), sodium carbonate (0.10 g, 0.9 mmol), dichlorobis(triphenylphosphine)-palladium(II) (30 mg, 0.05 mmol), and DMF (4 mL)-water (0.4 mL). The vial was sealed and placed in CEM microwave for 20 min at 130° C., with 100 Watts of power via Powermax. The reaction mixture was extracted with EtOAc (3×10 mL). The combined organic layers were dried over MgSO4 and concentrated (toluene was added in order to removed most of DMF). The crude product was purified using SiO2 chromatography (Teledyne Isco RediSep®, P/N 68-2203-026, 12 g SiO2, isocratic 5% MeOH in DCM with 1% AcOH, Flow=30 mL/min). The peak at 30 min was collected to afford the desired product as white solid (85 mg). MS (ESI pos. ion) m/z (M+1): 436.2. Calc'd exact mass for C23H18FN3O5: 357.41. 1H NMR (300 MHz, DMSO-d6) δ ppm 3.86 (s, 3 H) 4.70 (s, 4 H) 6.96-7.04 (m, 2 H) 7.13 (d, J=9.79 Hz, 1 H) 7.25-7.30 (m, 1 H) 7.69-7.73 (m, 1 H) 7.75 (s, 1 H) 7.86 (s, 1 H) 7.87-7.95 (m, 2 H) 8.12 (d, J=9.79 Hz, 1 H) 8.64 (d, J=5.26 Hz, 1 H).

後処理

  1. customThe vial was sealed
  2. extractionThe reaction mixture was extracted with EtOAc (3×10 mL)
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated
  5. addition(toluene was added in order to removed most of DMF)
  6. customThe crude product was purified
  7. customThe peak at 30 min was collected

出典と根拠

ORDレコード
ord-35d922f443054a80acefd589d1df3db5
出典データセット
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08314087B2

反応ノート

読み込み中…

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