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

HRID 1071279Notes

Reaction equation

HRID 1071279 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.C[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>[C:40]([O:39][C:37]([NH:36][CH:32]([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)[C:31]([OH:44])=[O:30])=[O:38])([CH3:43])([CH3:42])[CH3:41]

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 223978942-Tert-butoxycarbonylamino-3-[3-(1-{[4-(3-o-tolyl-ureido)-phenyl]-acetyl}-pyrrolidin-2-yl)-isoxazol-5-yl]-propionic acidYield 14.1%

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 (Cl) m/z 604.5 (M−1), 505.9 (M−99) C. 2-tert-Butoxycarbonylamino-pent-4-ynoic acid methyl ester

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-3cb6e6de4a924ab5b5745fd7f9153991
Source dataset
uspto-grants-2005_06
Patent number
US06903128B2

Reaction notes

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