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

HRID 1474682ノート

反応式

HRID 1474682 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:35])[CH2:25][C:26]2[CH:33]=[CH:32][C:31](O)=[CH:30][C:27]=2[C:28]#[N:29])[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:35])[CH2:25][C:26]2[CH:33]=[CH:32][C:31]([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:30][C:27]=2[C:28]#[N:29])[CH2:21][CH2:22][CH2:23]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 708186242-[2-(Azetidin-1-yl)-2-oxoethyl]-5-hydroxybenzonitrile

生成物 1

HCID 895839002-[2-(azetidin-1-yl)-2-oxoethyl]-5-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)benzonitrile

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 (22 mg, 0.076 mmol) was dissolved in toluene (1 ml) and 2-[2-(azetidin-1-yl)-2-oxoethyl]-5-hydroxybenzonitrile (15 mg, 0.069 mmol), triphenylphosphine (36 mg, 0.139 mmol), and DIAD (27 μl, 0.139 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 reside was purified by column chromatography using a Biotage SiO2 cartridge (25 g) using a gradient eluant of 10-100% EtOAc:hexanes to afford the title compound. LC/MS (m/z): 480 (M+H)+. GPR119 Human EC50: 0.32 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 reside was purified by column chromatography

出典と根拠

ORDレコード
ord-edd392ed50cb4002809d9c4265213166
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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