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 1474668Notes

Reaction equation

HRID 1474668 reaction equation
[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

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-a5b3aab5fb834594b36b858f44976164
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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