Cesium carbonate → 3-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[(1-methylethyl)oxy]-N-(5-methylpyrazin-2-yl)benzamide

HRID 1175942노트

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HRID 1175942 반응식
C(=O)([O-])[O-].[Cs+].[Cs+].[OH:7][C:8]1[CH:9]=[C:10]([CH:21]=[C:22]([O:24][CH:25]([CH3:27])[CH3:26])[CH:23]=1)[C:11]([NH:13][C:14]1[CH:19]=[N:18][C:17]([CH3:20])=[CH:16][N:15]=1)=[O:12].[N:28]1([C:32]([C:34]2[CH:39]=[CH:38][C:37](Br)=[CH:36][N:35]=2)=[O:33])[CH2:31][CH2:30][CH2:29]1>CC(N(C)C)=O>[N:28]1([C:32]([C:34]2[N:35]=[CH:36][C:37]([O:7][C:8]3[CH:9]=[C:10]([CH:21]=[C:22]([O:24][CH:25]([CH3:27])[CH3:26])[CH:23]=3)[C:11]([NH:13][C:14]3[CH:19]=[N:18][C:17]([CH3:20])=[CH:16][N:15]=3)=[O:12])=[CH:38][CH:39]=2)=[O:33])[CH2:31][CH2:30][CH2:29]1

참가 물질

5

반응물 3

HCID 10796Cesium carbonateHCID 536296172-(Azetidin-1-ylcarbonyl)-5-bromopyridineHCID 591271623-Hydroxy-N-(5-methylpyrazin-2-yl)-5-[(propan-2-yl)oxy]benzamide

생성물 1

HCID 160398643-{[6-(azetidin-1-ylcarbonyl)pyridin-3-yl]oxy}-5-[(1-methylethyl)oxy]-N-(5-methylpyrazin-2-yl)benzamide수율 32.2%

시약·촉매·용매 1

HCID 31374Dimethylacetamide용매

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온도
160 °C

실험 절차

Cesium carbonate (489 mg, 1.5 mmol) was added to a solution of 3-hydroxy-5-[(1-methylethyl)oxy]-N-(5-methylpyrazin-2-yl)benzamide (144 mg, 0.5 mmol) and 2-(azetidin-1-ylcarbonyl)-5-bromopyridine (181 mg, 0.75 mmol) and bromotris(triphenylphosphine)copper (93 mg, 0.1 mmol) in DMA (5 mL) and the stirred mixture heated at 160° C. in a microwave reactor for 4 hours. The mixture was cooled to RT and ambient pressure, partitioned between water (75 mL) and ethyl acetate (50 mL), the organic layer washed with brine, dried (MgSO4) and evaporated in vacuo. The residue was chromatographed on silica, eluting with 75% ethyl acetate in isohexane, to give the desired compound (crystallised from ether) (72 mg). 1H NMR δ (CDCl3): 1.3 (d, 6H), 2.3 (m, 2H), 2.5 (s, 3H), 4.2 (t, 2H), 4.5 (m, 1H), 4.65 (t, 2H), 6.7 (s, 1H), 7.05 (s, 1H), 7.2 (s, 1H), 7.3 (d, 1H), 8.0 (br, 2H), 8.3 (br, 2H) and 9.45 (s, 1H). m/z 448 (M+H)+. Mpt (melting onset) 125.7° C.

후처리

  1. temperatureThe mixture was cooled to RT
  2. customambient pressure, partitioned between water (75 mL) and ethyl acetate (50 mL)
  3. washthe organic layer washed with brine
  4. dry with materialdried (MgSO4)
  5. customevaporated in vacuo
  6. customThe residue was chromatographed on silica
  7. washeluting with 75% ethyl acetate in isohexane

출처 및 근거

ORD 기록
ord-015d56e880b1432ba43dc493eebd9e78
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07842694B2

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