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Cesium carbonate → 3-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

HRID 1011747
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HRID 1011747 반응식
[OH:1][C:2]1[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C@H:18]2[CH2:22][CH2:21][O:20][CH2:19]2)[CH:16]=1)[C:5]([NH:7][C:8]1[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=1)=[O:6].[N:23]1([C:27]([C:29]2[CH:34]=[N:33][C:32](Cl)=[CH:31][N:30]=2)=[O:28])[CH2:26][CH2:25][CH2:24]1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[N:23]1([C:27]([C:29]2[N:30]=[CH:31][C:32]([O:1][C:2]3[CH:3]=[C:4]([CH:14]=[C:15]([O:17][C@H:18]4[CH2:22][CH2:21][O:20][CH2:19]4)[CH:16]=3)[C:5]([NH:7][C:8]3[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=3)=[O:6])=[N:33][CH:34]=2)=[O:28])[CH2:26][CH2:25][CH2:24]1
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참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 46870328(Azetidin-1-yl)(5-chloropyrazin-2-yl)methanoneHCID 591271713-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide

생성물 1

HCID 160397273-{[5-(azetidin-1-ylcarbonyl)pyrazin-2-yl]oxy}-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide수율 31%

시약·촉매·용매 1

HCID 6342
Acetonitrile
용매

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온도
160 °C

실험 절차

A mixture of 3-hydroxy-N-(1-methyl-1H-pyrazol-3-yl)-5-[(3S)-tetrahydrofuran-3-yloxy]benzamide (80 mg, 0.26 mmol), 2-(azetidin-1-ylcarbonyl)-5-chloropyrazine (52 mg, 0.26 mmol) and caesium carbonate (172 mg, 0.53 mmol) in acetonitrile (3 mL) was stirred in a Smith Creator microwave at 160° C. for 1 hr. The solvent was removed in vacuo and ethyl acetate (50 mL) added to the residue. The organic phase was washed with water (20 mL), brine (50 mL), dried (MgSO4), filtered and the solvent removed in vacuo to give a yellow oil which was chromatographed on silica eluting with a gradient of 0-10% methanol in DCM to give the title compound (36 mg, 31%) as a white foam. This compound was crystallised from ethyl acetate and isohexane using vapour diffusion techniques. 1H NMR δ (CDCl3): 2.12-2.19 (1H, m), 2.21-2.28 (1H, m), 2.34-2.42 (2H, m), 3.75 (3H, s), 3.88-3.93 (1H, m), 3.98-4.02 (3H, m), 4.23 (2H, t), 4.69 (2H, t), 4.95-4.97 (1H, m), 6.80 (1H, d), 6.87 (1H, t), 7.23 (1H, d), 7.27-7.30 (1H, m), 7.28-7.30 (1H, m), 8.34 (1H, d), 8.84 (1H, d), 8.98 (1H, s); m/z 465 (M+H)+.

후처리

  1. customThe solvent was removed in vacuo and ethyl acetate (50 mL)
  2. additionadded to the residue
  3. washThe organic phase was 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 which
  8. customwas chromatographed on silica eluting with a gradient of 0-10% methanol in DCM

출처 및 근거

ORD 기록
ord-b9a85521cec34a3aa3a61ebd25544070
출처 데이터셋
uspto-grants-2011_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07977328B2

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