Triethylamine → 1-methylcyclopropyl 4-[(1R,2S)-2-(2-{4-[2-(dimethylamino)-2-oxoethyl]-2,5-difluorophenoxy}ethyl)cyclopropyl]piperidine-1-carboxylate

HRID 1850768Notes

Reaction equation

HRID 1850768 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][C@@H:11]2[CH2:13][C@@H:12]2[CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[C:5]([F:20])=[CH:4][C:3]=1[CH2:21][C:22]([N:24]([CH3:26])[CH3:25])=[O:23].C(N(CC)CC)C.[CH3:34][C:35]1([O:38][C:39](ON2C(=O)CCC2=O)=[O:40])[CH2:37][CH2:36]1>ClCCl>[CH3:25][N:24]([CH3:26])[C:22](=[O:23])[CH2:21][C:3]1[C:2]([F:1])=[CH:7][C:6]([O:8][CH2:9][CH2:10][C@@H:11]2[CH2:13][C@@H:12]2[CH:14]2[CH2:15][CH2:16][N:17]([C:39]([O:38][C:35]3([CH3:34])[CH2:37][CH2:36]3)=[O:40])[CH2:18][CH2:19]2)=[C:5]([F:20])[CH:4]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 577528092,5-Dioxopyrrolidin-1-yl 1-methylcyclopropyl carbonateHCID 867112002-(2,5-difluoro-4-{2-[(1S,2R)-2-piperidin-4 ylcyclopropyl]ethoxy}phenyl-)-N,N-dimethylacetamide

Product 1

HCID 708560251-methylcyclopropyl 4-[(1R,2S)-2-(2-{4-[2-(dimethylamino)-2-oxoethyl]-2,5-difluorophenoxy}ethyl)cyclopropyl]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(2,5-difluoro-4-{2-[(1S,2R)-2-piperidin-4 ylcyclopropyl]ethoxy}phenyl-)-N,N-dimethylacetamide (40.0 mg, 0.109 mmol) in 1 ml anhydrous dichloromethane at 0° C. was added triethylamine (0.0300 ml, 0.218 mmol) and 1-({[(1-methylcyclopropyl)oxy]carbonyl}oxy)pyrrolidine-2,5-dione (27.9 mg, 0.131 mmol). The reaction was stirred at RT for 2 hours. The solvent was evaporated, and the residue was purified by reverse-phase HPLC (SunFire Prep C18 OBD 5 um 19×100 mm column; 25-85% acetonitrile in 0.1% formic acid in water gradient) to give the title compound. LC/MS (m/z): 465.4 (M+H)+. Human EC50: 2.2 nM

Workup

  1. customThe solvent was evaporated
  2. customthe residue was purified by reverse-phase HPLC (SunFire Prep C18 OBD 5 um 19×100 mm column; 25-85% acetonitrile in 0.1% formic acid in water gradient)

Sources & evidence

ORD record
ord-47b9f1f581324dbc8d5b5acea98f0f4b
Source dataset
uspto-grants-2015_02
Patent number
US08957062B2

Reaction notes

Loading…