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Cesium carbonate → (S)-2-benzyl 3-ethyl 8-(6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-2-(methylsulfonyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate

HRID 1499185
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HRID 1499185 반응식
Cl[C:2]1[CH:7]=[C:6]([O:8][C@H:9]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=2[N:21]2[CH:25]=[CH:24][C:23]([CH3:26])=[N:22]2)[C:10]([F:13])([F:12])[F:11])[N:5]=[C:4]([S:27]([CH3:30])(=[O:29])=[O:28])[N:3]=1.[CH2:31]1[C:35]2([CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[CH2:34][CH:33]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[N:32]1[C:46]([O:48][CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)=[O:47].C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([C@@H:9]([O:8][C:6]2[N:5]=[C:4]([S:27]([CH3:30])(=[O:29])=[O:28])[N:3]=[C:2]([N:38]3[CH2:37][CH2:36][C:35]4([CH2:31][N:32]([C:46]([O:48][CH2:49][C:50]5[CH:51]=[CH:52][CH:53]=[CH:54][CH:55]=5)=[O:47])[C@H:33]([C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH2:34]4)[CH2:40][CH2:39]3)[CH:7]=2)[C:10]([F:12])([F:13])[F:11])=[C:15]([N:21]2[CH:25]=[CH:24][C:23]([CH3:26])=[N:22]2)[CH:16]=1
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HCID 10796Cesium carbonateHCID 1179417662-Benzyl 3-ethyl 2,8-diazaspiro[4.5]decane-2,3-dicarboxylateHCID 1179477694-chloro-6-[(1R)-1-[4-chloro-2-(3-methylpyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-methylsulfonylpyrimidine

생성물 1

HCID 117952025(S)-2-benzyl 3-ethyl 8-(6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-2-(methylsulfonyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate
수율 31.8%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

To a solution of 4-chloro-6-[(1R)-1-[4-chloro-2-(3-methylpyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]-2-methylsulfonylpyrimidine (2.49 g, 5.17 mmol) in dioxane (100 mL) was added 2-benzyl 3-ethyl 2,8-diazaspiro[4.5]decane-2,3-dicarboxylate (1.8 g, 5.2 mmol), Cs2CO3 (5.06 g, 15.5 mmol), and the reaction mixture was heated to 100° C. for 1.5 h. The reaction mixture was cooled to RT, quenched with brine, and extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Purification on a 120 g Isco RediSep silica cartridge (EtOAc:heptane) provided (S)-2-benzyl 3-ethyl 8-(6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)-2-(methylsulfonyl)pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate as a white solid (1.3 g) in addition to (S)-2-benzyl 3-ethyl 8-(4-chloro-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-2-yl)-2,8-diazaspiro[4.5]decane-2,3-dicarboxylate.

후처리

  1. temperatureThe reaction mixture was cooled to RT
  2. customquenched with brine
  3. extractionextracted with EtOAc
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification on a 120 g Isco RediSep silica cartridge (EtOAc:heptane)

출처 및 근거

ORD 기록
ord-52e6a8f77a2248a7b4948ba863703513
출처 데이터셋
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09199994B2

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