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Water → tert-butyl (2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)(3-methyl-5-nitropyridin-2-yl)carbamate

HRID 1039074
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HRID 1039074 반응식
CC1C=CC(S(O[CH2:12][CH2:13][C@@H:14]2[CH2:16][C@@H:15]2[CH:17]2[CH2:22][CH2:21][N:20]([C:23]3[N:28]=[CH:27][C:26]([Cl:29])=[CH:25][N:24]=3)[CH2:19][CH2:18]2)(=O)=O)=CC=1.[CH3:30][C:31]1[C:32]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[N:33][CH:34]=[C:35]([N+:37]([O-:39])=[O:38])[CH:36]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[Cl:29][C:26]1[CH:27]=[N:28][C:23]([N:20]2[CH2:19][CH2:18][CH:17]([C@H:15]3[CH2:16][C@H:14]3[CH2:13][CH2:12][N:40]([C:32]3[C:31]([CH3:30])=[CH:36][C:35]([N+:37]([O-:39])=[O:38])=[CH:34][N:33]=3)[C:41](=[O:47])[O:42][C:43]([CH3:44])([CH3:45])[CH3:46])[CH2:22][CH2:21]2)=[N:24][CH:25]=1
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참가 물질

6

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 67962193Tert-butyl (3-methyl-5-nitropyridin-2-yl)carbamateHCID 866661412-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonate

생성물 1

HCID 67962326tert-butyl (2-{(1S,2S)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl)(3-methyl-5-nitropyridin-2-yl)carbamate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
50 °C

실험 절차

2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethyl 4-methylbenzenesulfonate (95 mg, 0.22 mmol) from Step 1 of Example 2 and tert-butyl (3-methyl-5-nitropyridin-2-yl)carbamate (55 mg, 0.22 mmol) were added in DMF (2.2 mL), then cesium carbonate (212 mg, 0.65=101) was added and the reaction was heated to 50° C. overnight. The reaction was cooled to room temperature, water (20 mL) was added and extracted with ethyl acetate (50 mL), second wash with brine (20 mL). The organic phase was dried by magnesium sulfate, filtered, concentrated and purified by column chromatography through a 25 gram Biotage SNAP KP-Sil™ silica gel cartridge eluting with 6.3% ethyl acetate/hexanes to give the title compound as a pale yellow sticky solid.

후처리

  1. temperatureThe reaction was cooled to room temperature
  2. extractionextracted with ethyl acetate (50 mL)
  3. washsecond wash with brine (20 mL)
  4. dry with materialThe organic phase was dried by magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by column chromatography through a 25 gram Biotage SNAP KP-Sil™ silica gel cartridge
  8. washeluting with 6.3% ethyl acetate/hexanes

출처 및 근거

ORD 기록
ord-cc3d5011be624a4399b9e5e4ef1b4905
출처 데이터셋
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08552022B2

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