Triethylamine → 2-Tert-butoxycarbonylamino-3-[3-(1-{[4-(3-o-tolyl-ureido)-phenyl]-acetyl}-pyrrolidin-2-yl)-isoxazol-5-yl]-propionic acid methyl ester

HRID 433666Notes

Reaction equation

HRID 433666 reaction equation
[OH:1][N:2]=[CH:3][CH:4]1[CH2:8][CH2:7][CH2:6][N:5]1[C:9](=[O:28])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([NH:17][C:18]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=2[CH3:27])=[O:19])=[CH:13][CH:12]=1.[CH3:29][O:30][C:31](=[O:44])[CH:32]([NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:33][C:34]#[CH:35].C(N(CC)CC)C.Cl[O-].[Na+]>ClCCl>[CH3:29][O:30][C:31](=[O:44])[CH:32]([NH:36][C:37]([O:39][C:40]([CH3:42])([CH3:41])[CH3:43])=[O:38])[CH2:33][C:34]1[O:1][N:2]=[C:3]([CH:4]2[CH2:8][CH2:7][CH2:6][N:5]2[C:9](=[O:28])[CH2:10][C:11]2[CH:12]=[CH:13][C:14]([NH:17][C:18]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[CH3:27])=[O:19])=[CH:15][CH:16]=2)[CH:35]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 10537281Methyl 2-[(tert-butoxycarbonyl)amino]pent-4-ynoateHCID 23665760Sodium HypochloriteHCID 879728581-(4-{2-[2-(Hydroxyimino-methyl)-pyrrolidin-1-yl]-2-oxo-ethyl}-phenyl)-3-o-tolyl-urea

Product 1

HCID 206103042-Tert-butoxycarbonylamino-3-[3-(1-{[4-(3-o-tolyl-ureido)-phenyl]-acetyl}-pyrrolidin-2-yl)-isoxazol-5-yl]-propionic acid methyl esterYield 14%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(4-{2-[2-(hydroxyimino-methyl)-pyrrolidin-1-yl]-2-oxo-ethyl}-phenyl)-3-o-tolyl-urea (300 mg, 0.789 mmol), 2-tert-butoxycarbonylamino-pent-4-ynoic acid methyl ester (359 mg, 1.182 mmol, crude mixture) and triethyl amine (12.9 μL) in dichloromethane (2 mL) was stirred 5 minutes. A sodium hypochlorite solution (5.25%, 2 mL) was added. The reaction was stirred at room temperature overnight. The aqueous portion was extracted 4 times with dichloromethane. The combined organic portions were washed with brine, dried over magnesium sulfate and concentrated. Chromatography of the crude mixture on a Biotage Flash 40S column eluting with ethyl acetate/hexane 1:5 gave the title compound (66 mg, 14%). MS (CI) m/z 604.5 (M−1), 505.9 (M-99)

Workup

  1. extractionThe aqueous portion was extracted 4 times with dichloromethane
  2. washThe combined organic portions were washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. washChromatography of the crude mixture on a Biotage Flash 40S column eluting with ethyl acetate/hexane 1:5

Sources & evidence

ORD record
ord-5fe9ca639e4f4fc382497bdf18fb5f5c
Source dataset
uspto-grants-2003_12
Patent number
US06667331B2

Reaction notes

Loading…