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Water → 1-[4-(3,4-Difluoro-1H-pyrrol-1-yl)-2-fluorophenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1895341
ノート
印刷プレビュー

反応式

HRID 1895341 の反応式
CC([O-])(C)C.[K+].[F:7][C:8]1[CH:13]=[C:12]([N:14]2[CH2:18][C:17](F)([F:19])[C:16](F)([F:21])[CH2:15]2)[CH:11]=[CH:10][C:9]=1[N:23]1[CH:28]=[C:27]([O:29][CH3:30])[C:26](=[O:31])[C:25]([C:32]2[N:36]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[N:35]=[CH:34][CH:33]=2)=[N:24]1.O>CS(C)=O>[F:21][C:16]1[C:17]([F:19])=[CH:18][N:14]([C:12]2[CH:11]=[CH:10][C:9]([N:23]3[CH:28]=[C:27]([O:29][CH3:30])[C:26](=[O:31])[C:25]([C:32]4[N:36]([C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)[N:35]=[CH:34][CH:33]=4)=[N:24]3)=[C:8]([F:7])[CH:13]=2)[CH:15]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 3

HCID 962WaterHCID 23665647Potassium tert-butoxideHCID 468487401-[2-fluoro-4-(3,3,4,4-tetrafluoropyrrolidin-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

生成物 1

HCID 468489141-[4-(3,4-Difluoro-1H-pyrrol-1-yl)-2-fluorophenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one収率 32.4%

試薬・触媒・溶媒 1

HCID 679
Dimethyl Sulfoxide
溶媒

実験手順

KOtBu (236 mg, 2.1 mmol) was added portionwise at room temperature to a solution of 1-[2-fluoro-4-(3,3,4,4-tetrafluoropyrrolidin-1-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one (352 mg, 0.7 mmol) in DMSO (3.5 mL). After stirring for 30 min, the reaction mixture was poured into water and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was subjected to basic silica gel column chromatography eluting with hexane/AcOEt (1/1-0/1) followed by purification by preparative HPLC. Recrystallization from MeOH/H2O afforded the title compound (105 mg, 32% yield) as a white solid: mp 212-214° C.; 1H NMR (300 MHz, CDCl3): δ ppm 3.91 (3H, s), 6.42 (1H, t, J=9.0 Hz), 6.68-6.78 (2H, m), 6.87 (1H, ddd, J=1.1, 2.6, 9.0 Hz), 7.07 (1H, dd, J=2.6, 12.4 Hz), 7.33 (1H, d, J=2.3 Hz), 7.36-7.48 (5H, m), 7.78-7.79 (2H, m). LC-MS (ESI) m/z 464 [M+H]+. Anal. Calcd for C24H16F3N5O2: C, 62.20; H, 3.48; N, 15.11. Found: C, 62.20; H, 3.51; N, 15.01.

後処理

  1. extractionextracted with AcOEt
  2. washThe extract was washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. washeluting with hexane/AcOEt (1/1-0/1)
  6. customfollowed by purification by preparative HPLC
  7. customRecrystallization from MeOH/H2O

出典と根拠

ORDレコード
ord-740f6cef9bbf49fd976f7553b7b72d48
出典データセット
uspto-grants-2013_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08513251B2

反応ノート

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