Triphenylphosphine → 4-((1R,2S)-2-{2-[4-(2-azetidin-1-yl-2-oxoethyl)-2-fluorophenoxy]ethyl}cyclopropyl)-1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidine

HRID 1850780Notes

Reaction equation

HRID 1850780 reaction equation
[N:1]1([C:5](=[O:15])[CH2:6][C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[C:9]([F:14])[CH:8]=2)[CH2:4][CH2:3][CH2:2]1.[CH:16]([C:19]1[N:23]=[C:22]([N:24]2[CH2:29][CH2:28][CH:27]([C@H:30]3[CH2:32][C@H:31]3[CH2:33][CH2:34]O)[CH2:26][CH2:25]2)[O:21][N:20]=1)([CH3:18])[CH3:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>ClCCl>[N:1]1([C:5](=[O:15])[CH2:6][C:7]2[CH:12]=[CH:11][C:10]([O:13][CH2:34][CH2:33][C@@H:31]3[CH2:32][C@@H:30]3[CH:27]3[CH2:26][CH2:25][N:24]([C:22]4[O:21][N:20]=[C:19]([CH:16]([CH3:17])[CH3:18])[N:23]=4)[CH2:29][CH2:28]3)=[C:9]([F:14])[CH:8]=2)[CH2:4][CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 97268Di-tert-butyl azodicarboxylateHCID 708186512-((1S,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)ethanolHCID 708191321-(Azetidin-1-yl)-2-(3-fluoro-4-hydroxyphenyl)ethanone

Product 1

HCID 708185064-((1R,2S)-2-{2-[4-(2-azetidin-1-yl-2-oxoethyl)-2-fluorophenoxy]ethyl}cyclopropyl)-1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(azetidin-1-yl)-2-(3-fluoro-4-hydroxyphenyl)ethanone (65.0 mg, 0.236 mmol) in 5 ml anhydrous dichloromethane at RT was added a solution of 2-{(1S,2R)-2-[1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl]cyclopropyl}ethanol (59.0 mg, 0.283 mmol), triphenylphosphine, polymer-bound (186 mg, 0.534 mmol), and di-tert-butyl azodicarboxylate (109 mg, 0.472 mmol). The reaction mixture as stirred at RT for 3 hours. The mixture was filtered by Celite and concentrated. The residue The reaction mixture was filtered and purified by reverse-phase HPLC (SunFire Prep C18 OBD 5 um 19×100 mm column; 35-100% acetonitrile in 0.1% formic acid in water gradient), to give the title compound. LC/MS (m/z) 471.3 (M+H)+. Human EC50: 5.3 nM

Workup

  1. filtrationThe mixture was filtered by Celite
  2. concentrationconcentrated
  3. filtrationThe residue The reaction mixture was filtered
  4. custompurified by reverse-phase HPLC (SunFire Prep C18 OBD 5 um 19×100 mm column; 35-100% acetonitrile in 0.1% formic acid in water gradient)

Sources & evidence

ORD record
ord-51c681f01f1b463180fa7652bea59005
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

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