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Diethyl Ether → N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide methanesulfonate

HRID 1050864
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HRID 1050864 반응식
[CH:1]1([C:4]([NH:6][C:7]2[CH:12]=[C:11]([O:13][C:14]3[C:19]([F:20])=[CH:18][C:17]([NH:21][C:22]([C:24]4[C:25](=[O:40])[N:26]([C:33]5[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=5)[CH:27]=[CH:28][C:29]=4[O:30][CH2:31][CH3:32])=[O:23])=[C:16]([F:41])[CH:15]=3)[CH:10]=[CH:9][N:8]=2)=[O:5])[CH2:3][CH2:2]1.[CH3:42][S:43]([OH:46])(=[O:45])=[O:44].CCOCC>CC#N>[CH3:42][S:43]([OH:46])(=[O:45])=[O:44].[CH:1]1([C:4]([NH:6][C:7]2[CH:12]=[C:11]([O:13][C:14]3[C:19]([F:20])=[CH:18][C:17]([NH:21][C:22]([C:24]4[C:25](=[O:40])[N:26]([C:33]5[CH:34]=[CH:35][C:36]([F:39])=[CH:37][CH:38]=5)[CH:27]=[CH:28][C:29]=4[O:30][CH2:31][CH3:32])=[O:23])=[C:16]([F:41])[CH:15]=3)[CH:10]=[CH:9][N:8]=2)=[O:5])[CH2:3][CH2:2]1
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HCID 3283Diethyl EtherHCID 6395Methanesulfonic AcidHCID 71575771N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

생성물 1

HCID 86703362N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide methanesulfonate수율 44.5%

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
80 °C

실험 절차

A suspension of N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide (0.029 g, 0.051 mmol) in MeCN (0.5 mL) was heated to 80° C., treated with methanesulfonic acid (3.34 μl, 0.051 mmol), then cooled to RT and stirred overnight. Ether was added drop wise until solids precipitated. The mixture was stirred for several hours. The solids were collected by filtration, rinsed with ether and dried under vacuum to afford N-(4-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)-2,5-difluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide methanesulfonate (15 mg, 44% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.22 (s, 1 H), 10.99 (s, 1 H), 8.33 (dd, J=12.6, 7.2 Hz, 1 H), 8.20 (d, J=5.8 Hz, 1 H), 7.92 (d, J=7.8 Hz, 1 H), 7.63-7.45 (m, 4 H), 7.36 (m, 2 H), 6.79 (d, J=5.7 Hz, 1 H), 6.55 (d, J=7.9 Hz, 1 H), 4.28 (q, J=7.0 Hz, 2 H), 2.29 (s, 3 H), 1.93 (m, 1 H), 1.33 (t, J=7.0 Hz, 3 H), 0.77 (m, 4 H); MS (ESI) m/z: 565.2 (M+H+).

후처리

  1. temperaturecooled to RT
  2. customprecipitated
  3. stirringThe mixture was stirred for several hours
  4. filtrationThe solids were collected by filtration
  5. washrinsed with ether
  6. customdried under vacuum

출처 및 근거

ORD 기록
ord-44b3200e864e422f97efcf0cbcdd7b08
출처 데이터셋
uspto-grants-2016_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09387202B2

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