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 1474668ノート

反応式

HRID 1474668 の反応式
[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

参加物

7

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-a5b3aab5fb834594b36b858f44976164
出典データセット
uspto-grants-2015_04
特許番号
US09018224B2

反応ノート

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