Lithium Hydroxide → (2S,3S)-3-((S)-1-((1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)methylamino)-1-oxo-3-(thiazol-4-yl)propan-2-ylcarbamoyl)oxirane-2-carboxylic acid

HRID 1478653Notes

Reaction equation

HRID 1478653 reaction equation
C([O:3][C:4]([C@@H:6]1[C@@H:8]([C:9](=[O:34])[NH:10][C@@H:11]([CH2:28][C:29]2[N:30]=[CH:31][S:32][CH:33]=2)[C:12]([NH:14][CH2:15][C:16]2[N:17]=[N:18][N:19]([C:21]3[CH:26]=[CH:25][C:24]([Br:27])=[CH:23][CH:22]=3)[CH:20]=2)=[O:13])[O:7]1)=[O:5])C.[Li+].[OH-]>>[Br:27][C:24]1[CH:23]=[CH:22][C:21]([N:19]2[CH:20]=[C:16]([CH2:15][NH:14][C:12](=[O:13])[C@@H:11]([NH:10][C:9]([C@H:8]3[O:7][C@@H:6]3[C:4]([OH:5])=[O:3])=[O:34])[CH2:28][C:29]3[N:30]=[CH:31][S:32][CH:33]=3)[N:17]=[N:18]2)=[CH:26][CH:25]=1

Participants

3

Reactant 2

HCID 3939Lithium HydroxideHCID 131736515(2S,3S)-ethyl-3-((S)-1-((1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)methylamino)-1-oxo-3-(thiazol-4-yl)propan-2-ylcarbamoyl)oxirane-2-carboxylate

Product 1

HCID 71818085(2S,3S)-3-((S)-1-((1-(4-bromophenyl)-1H-1,2,3-triazol-4-yl)methylamino)-1-oxo-3-(thiazol-4-yl)propan-2-ylcarbamoyl)oxirane-2-carboxylic acidYield 86.3%

Procedure

Followed general procedure using: the corresponding peptidomimetic epoxide ethyl ester 44 (25 mg, 0.04 mmol); LiOH (1.1 mg, 0.04 mmol); after extraction afforded the desired product as a white solid (18 mg, 75.9%). 1H NMR (DMSO-d6, 400 MHz): δ 8.99-8.98 (d, 1H, J=1.87 Hz); 8.74-8.71 (t, 1H); 8.58-8.56 (d, 1H, J=8.27 Hz); 8.54 (s, 1H); 7.86-7.79 (q, 4H); 7.34-7.33 (d, 1H, J=1.75 Hz); 4.70-4.65 (q, 1H); 4.40-4.38 (d, 2H, J=5.59 Hz); 3.60-3.59 (d, 1H, J=1.77 Hz); 3.38-3.37 (d, 1H, J=1.77 Hz); 3.28-3.10 (m, 2H). 13C NMR (DMSO-d6, 100 MHz): 170.62, 169.08, 165.74, 154.06, 153.29, 146.57, 136.25, 133.27, 122.31, 121.67, 121.54, 116.20, 53, 25, 52.94, 51.89, 34.76, 33.49. HRMS-ESI: m/z [M+H+] calculated for C19H17BrN6O5S: 521.34, observed: m/z 523.0229 (M+H+); m/z 519.0123 (M−H+); HPLC Method 2: Rt=21.8 min; 97.2%.

Workup

  1. extractionafter extraction

Sources & evidence

ORD record
ord-c353892934674b548ed5aa602f1afbb4
Source dataset
uspto-grants-2016_08
Patent number
US09403843B2

Reaction notes

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