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

HRID 1474687Notes

Reaction equation

HRID 1474687 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:35])[CH2:25][C:26]2[CH:31]=[CH:30][C:29](O)=[CH:28][C:27]=2[O:33][CH3:34])[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>[N:20]1([C:24](=[O:35])[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[O:33][CH3:34])[CH2:23][CH2:22][CH2:21]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 581286112-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanolHCID 895816361-(Azetidin-1-yl)-2-(4-hydroxy-2-methoxyphenyl)ethanone

Product 1

HCID 895838391-(azetidin-1-yl)-2-[4-(2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethoxy)-2-methoxyphenyl]ethanone

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

2-{(1S,2R)-2-[1-(5-chloropyrimidin-2-yl)piperidin-4-yl]cyclopropyl}ethanol (75 mg, 0.266 mmol) was dissolved in toluene (1 ml) and 1-(azetidin-1-yl)-2-(4-hydroxy-2-methoxyphenyl)ethanone (59 mg, 0.069 mmol), triphenylphosphine (105 mg, 0.399 mmol), and DIAD (78 μl, 0.399 mmol) added and the mixture stirred at RT overnight. The mixture was concentrated in vacuo and the residue purified by column chromatography using a Biotage RP C18 cartridge (30 g) using a gradient eluant of 0-100% water:acetonitrile+0.1% TFA to afford the title compound. LC/MS (m/z): 485 (M+H)+. GPR119 Human EC50: 7.1 nM.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customthe residue purified by column chromatography

Sources & evidence

ORD record
ord-caf7366f68f24c21a244ece5bf12867e
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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