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 1474682Notes

Reaction equation

HRID 1474682 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: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

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-edd392ed50cb4002809d9c4265213166
Source dataset
uspto-grants-2015_04
Patent number
US09018224B2

Reaction notes

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