Triphenylphosphine → 1-(azetidin-1-yl)-2-[4-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-methylphenyl]ethanone

HRID 1474668노트

반응식

HRID 1474668 반응식
[Cl:1][C:2]1[CH:3]=[N:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([C@H:14]3[CH2:16][C@H:15]3[CH2:17][CH2:18][OH:19])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[N:20]1([C:24](=[O:34])[CH2:25][C:26]2[CH:31]=[CH:30][C:29](O)=[CH:28][C:27]=2[CH3:33])[CH2:23][CH2:22][CH2:21]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1(C)C=CC=CC=1.C(OCC)(=O)C>[N:20]1([C:24](=[O:34])[CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:19][CH2:18][CH2:17][C@@H:15]3[CH2:16][C@@H:14]3[CH:11]3[CH2:12][CH2:13][N:8]([C:5]4[N:6]=[CH:7][C:2]([Cl:1])=[CH:3][N:4]=4)[CH2:9][CH2:10]3)=[CH:28][C:27]=2[CH3:33])[CH2:23][CH2:22][CH2:21]1

참가 물질

7

반응물 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 581286112-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanolHCID 708187231-(Azetidin-1-yl)-2-(4-hydroxy-2-methylphenyl)ethanone

생성물 1

HCID 895838751-(azetidin-1-yl)-2-[4-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-methylphenyl]ethanone

시약·촉매·용매 2

HCID 1140Toluene용매HCID 8857Ethyl Acetate용매

실험 절차

2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol (50 mg, 0.177 mmol) was dissolved in toluene (1 ml) and 1-(azetidin-1-yl)-2-(4-hydroxy-2-methylphenyl)ethanone (36.4 mg, 0.177 mmol), triphenylphosphine (55.8 mg, 0.213 mmol), and DIAD (41.4 μl, 0.213 mmol) added and the mixture stirred at RT overnight. The mixture was diluted with ethyl acetate (20 mL), washed with brine (10 ml), dried over MgSO4, filtered and the solvent removed in vacuo. The residue was purified by chromatography on silica gel, Biotage 25M, eluting with a gradient eluant of 0-100% EtOAc/Hexane to afford afford the title compound. LC/MS (m/z): 469 (M+H)+. GPR119 Human EC50: 0.73 nM.

후처리

  1. washwashed with brine (10 ml)
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customthe solvent removed in vacuo
  5. customThe residue was purified by chromatography on silica gel, Biotage 25M
  6. washeluting with a gradient eluant of 0-100% EtOAc/Hexane
  7. customto afford

출처 및 근거

ORD 기록
ord-a5b3aab5fb834594b36b858f44976164
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018224B2

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