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Potassium Carbonate → 3-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-({(1S)-2-[(difluoromethyl)oxy]-1-methylethyl}oxy)-N-(1-methyl-1H-pyrazol-3-yl)benzamide

HRID 1011718
ノート
印刷プレビュー

反応式

HRID 1011718 の反応式
[F:1][CH:2]([F:24])[O:3][CH2:4][C@@H:5]([O:7][C:8]1[CH:9]=[C:10]([CH:20]=[C:21]([OH:23])[CH:22]=1)[C:11]([NH:13][C:14]1[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=1)=[O:12])[CH3:6].[N:25]1([C:29]([C:31]2[CH:32]=[C:33]([Cl:38])[C:34](Cl)=[N:35][CH:36]=2)=[O:30])[CH2:28][CH2:27][CH2:26]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[N:25]1([C:29]([C:31]2[CH:32]=[C:33]([Cl:38])[C:34]([O:23][C:21]3[CH:20]=[C:10]([CH:9]=[C:8]([O:7][C@@H:5]([CH3:6])[CH2:4][O:3][CH:2]([F:1])[F:24])[CH:22]=3)[C:11]([NH:13][C:14]3[CH:18]=[CH:17][N:16]([CH3:19])[N:15]=3)=[O:12])=[N:35][CH:36]=2)=[O:30])[CH2:28][CH2:27][CH2:26]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

5

反応物 3

HCID 11430Potassium CarbonateHCID 536296165-(Azetidin-1-ylcarbonyl)-2,3-dichloropyridineHCID 591271223-[(2S)-1-(difluoromethoxy)propan-2-yl]oxy-5-hydroxy-N-(1-methylpyrazol-3-yl)benzamide

生成物 1

HCID 160396463-{[5-(azetidin-1-ylcarbonyl)-3-chloropyridin-2-yl]oxy}-5-({(1S)-2-[(difluoromethyl)oxy]-1-methylethyl}oxy)-N-(1-methyl-1H-pyrazol-3-yl)benzamide収率 53.6%

試薬・触媒・溶媒 1

HCID 6342
Acetonitrile
溶媒

反応条件

温度
160 °C

実験手順

A mixture of 3-({(1S)-2-[(difluoromethyl)oxy]-1-methylethyl}oxy)-5-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)benzamide (110 mg, 0.32 mmol), 5-(azetidin-1-ylcarbonyl)-2,3-dichloropyridine (75 mg, 0.32 mmol) and potassium carbonate (89 mg, 0.64 mmol) in acetonitrile (5 mL) was stirred in a ‘Biotage initiator Microwave’ at 160° C. for 3 hours. The solvent was removed in vacuo and ethyl acetate (50 mL) added to the residue which was washed with water (20 mL), brine (50 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a yellow oil. The residue was chromatographed on silica, eluting with a gradient of 50-100% ethyl acetate in isohexane, to give the desired compound (92 mg). 1H NMR δ (CDCl3): 1.40 (d, 3H), 2.41 (quin, 2H), 3.81 (s, 3H), 4.01 (mult, 2H), 4.26 (t, 2H), 4.38 (t, 2H), 4.67 (sextet, 1H), 6.29 (t, 1H), 6.82 (d, 1H), 6.96 (t, 1H), 7.27 (t, 1H), 7.31 (d, 1H), 7.38 (t, 1H), 8.18 (d, 1H), 8.26 (d, 1H), 8.77 (s, 1H), m/z 536 (M+H)+

後処理

  1. customThe solvent was removed in vacuo and ethyl acetate (50 mL)
  2. additionadded to the residue which
  3. washwas washed with water (20 mL), brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent removed in vacuo
  7. customto give a yellow oil
  8. customThe residue was chromatographed on silica
  9. washeluting with a gradient of 50-100% ethyl acetate in isohexane

出典と根拠

ORDレコード
ord-385ec12a537e4ce793c3b9732b106ad9
出典データセット
uspto-grants-2011_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07977328B2

反応ノート

読み込み中…

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