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Diisopropylethylamine → [2-(2-Fluoro-6-methoxy-phenyl)-thiazol-4-yl]-(2-methyl-piperidin-1-yl)-methanone

HRID 1990994
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HRID 1990994 반응식
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[C:3]=1[C:10]1[S:11][CH:12]=[C:13]([C:15]([OH:17])=O)[N:14]=1.[CH2:18]1[C@H:27]2[C@@H:22](CCCC2)[CH2:21][CH2:20][NH:19]1.[CH3:28]CN(C(C)C)C(C)C.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][CH3:9])[C:3]=1[C:10]1[S:11][CH:12]=[C:13]([C:15]([N:19]2[CH2:18][CH2:27][CH2:22][CH2:21][CH:20]2[CH3:28])=[O:17])[N:14]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 11083964trans-DecahydroisoquinolineHCID 589248452-(2-Fluoro-6-methoxy-phenyl)-thiazole-4-carboxylic acid

생성물 1

HCID 58924834[2-(2-Fluoro-6-methoxy-phenyl)-thiazol-4-yl]-(2-methyl-piperidin-1-yl)-methanone수율 17.9%

시약·촉매·용매 2

HCID 962
Water
용매
HCID 6344Dichloromethane용매

실험 절차

2-(2-Fluoro-6-methoxy-phenyl)-thiazole-4-carboxylic acid (49.5 mg, 0.2 mmol) from the previous step, trans-decahydro-isoquinoline (TCI America, Portland, Oreg.; 27.8 mg, 0.2 mmol), DIPEA (0.1 mL, 0.57 mmol), and PyBrop (103 mg, 0.22 mmol) were mixed in dry DCM (1 mL) and the mixture was left stirring for overnight at room temperature. To the mixture was added water. The DCM layer was separated and the aqueous layer was extracted with DCM twice. The combined DCM layers were dried under vacuum and purified by C-18 reversed phase HPLC with a gradient of 10-100% Acetonitrile/water to give [2-(2-fluoro-6-methoxy-phenyl)-thiazol-4-yl]-(2-methyl-piperidin-1-yl)-methanone (12 mg, 16%).

후처리

  1. waitthe mixture was left
  2. customThe DCM layer was separated
  3. extractionthe aqueous layer was extracted with DCM twice
  4. dry with materialThe combined DCM layers were dried under vacuum
  5. custompurified by C-18

출처 및 근거

ORD 기록
ord-294ddf8108ee4196baab1c4ee00a1295
출처 데이터셋
uspto-grants-2010_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07645773B2

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