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Acetic Acid → 1-(5-{3-[(4-Cyclobutylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutanol

HRID 1040138
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HRID 1040138 반응식
Cl[C:2]1[N:7]=[C:6]([CH:8]2[CH2:11][CH2:10][CH2:9]2)[CH:5]=[CH:4][N:3]=1.[NH2:12][C:13]1[CH:14]=[C:15]([C:20]2[S:24][C:23]([C:25]3([OH:29])[CH2:28][CH2:27][CH2:26]3)=[N:22][CH:21]=2)[CH:16]=[C:17]([CH3:19])[CH:18]=1.C(O)(=O)C>O1CCOCC1>[CH:8]1([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:12][C:13]3[CH:14]=[C:15]([C:20]4[S:24][C:23]([C:25]5([OH:29])[CH2:28][CH2:27][CH2:26]5)=[N:22][CH:21]=4)[CH:16]=[C:17]([CH3:19])[CH:18]=3)[N:7]=2)[CH2:11][CH2:10][CH2:9]1
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참가 물질

5

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HCID 176Acetic AcidHCID 497584742-Chloro-4-cyclobutylpyrimidineHCID 584563951-[5-(3-Amino-5-methylphenyl)-1,3-thiazol-2-yl]cyclobutanol

생성물 1

HCID 584560801-(5-{3-[(4-Cyclobutylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutanol수율 44%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

2-Chloro-4-cyclobutylpyrimidine (65 mg, 0.39 mmol), Intermediate 15 (100 mg, 0.39 mmol), and acetic acid (22 μL, 0.39 mmol) were combined in dioxane (1.9 mL) and the mixture was stirred at 120° C. for 3 h. The mixture was cooled to room temperature and directly purified by Combiflash chromatography on silica gel, eluting with ethyl acetate/isohexane to provide 66 mg (0.17 mmol, 44%) of 1-(5-{3-[(4-cyclobutylpyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)cyclobutanol. MS ESI: [M+H]+ m/z 393.2. 1H NMR (600 MHz, DMSO-d6) δ 9.56 (s, 1H), 8.33 (d, J=4.8, 1H), 8.12 (s, 1H), 7.95 (s, 1H), 7.48 (s, 1H), 7.05 (s, 1H), 6.68 (d, J=5.4, 1H), 6.46 (s, 1H), 3.53-3.50 (m, 1H), 2.52-2.46 (m, 2H), 2.33-2.22 (m, 9H), 1.99 (m, 1H), 1.87-1.83 (m, 3H). rhSYK activity=+++

후처리

  1. temperatureThe mixture was cooled to room temperature
  2. customdirectly purified by Combiflash chromatography on silica gel
  3. washeluting with ethyl acetate/isohexane

출처 및 근거

ORD 기록
ord-32246bf22e384639afb319b6b5bc26dd
출처 데이터셋
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08551984B2

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