Lithium Hydroxide → (2S,3S)-3-((S)-1-((1-(2,6-difluorophenyl)-1H-1,2,3-triazol-4-yl)methylamino)-1-oxo-3-(thiazol-4-yl)propan-2-ylcarbamoyl)oxirane-2-carboxylic acid

HRID 1478655Notes

Reaction equation

HRID 1478655 reaction equation
C([O:3][C:4]([C@@H:6]1[C@@H:8]([C:9](=[O:35])[NH:10][C@@H:11]([CH2:29][C:30]2[N:31]=[CH:32][S:33][CH:34]=2)[C:12]([NH:14][CH2:15][C:16]2[N:17]=[N:18][N:19]([C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])[CH:20]=2)=[O:13])[O:7]1)=[O:5])C.[Li+].[OH-]>>[F:27][C:26]1[CH:25]=[CH:24][CH:23]=[C:22]([F:28])[C:21]=1[N:19]1[CH:20]=[C:16]([CH2:15][NH:14][C:12](=[O:13])[C@@H:11]([NH:10][C:9]([C@H:8]2[O:7][C@@H:6]2[C:4]([OH:5])=[O:3])=[O:35])[CH2:29][C:30]2[N:31]=[CH:32][S:33][CH:34]=2)[N:17]=[N:18]1

Participants

3

Reactant 2

HCID 3939Lithium HydroxideHCID 131736517(2S,3S)-ethyl-3-((S)-1-((1-(2,6-difluorophenyl)-1H-1,2,3-triazol-4-yl)methylamino)-1-oxo-3-(thiazol-4-yl)propan-2-ylcarbamoyl)oxirane-2-carboxylate

Product 1

HCID 71818226(2S,3S)-3-((S)-1-((1-(2,6-difluorophenyl)-1H-1,2,3-triazol-4-yl)methylamino)-1-oxo-3-(thiazol-4-yl)propan-2-ylcarbamoyl)oxirane-2-carboxylic acid

Procedure

Followed general procedure using: the corresponding peptidomimetic epoxide ethyl ester 46 (2.4 mg, 0.05 mmol); LiOH (1.1 mg, 0.05 mmol); after extraction afforded the desired product as a while solid (13 mg, 57.3%). 1H NMR (DMSO-d6, 400 MHz): δ 9.00-8.99 (d, 1H, J=1.90 Hz); 8.78-8.76 (t, 1H); 8.60-8.58 (d, 1H, J=8.29 Hz); 8.27 (s, 1H); 7.77-7.69 (m, 1H); 7.49-7.45 (t, 2H); 7.36-7.27 (m, 2H); 4.71-4.65 (m, 1H); 4.44-4.42 (d, 2H, J=5.63 Hz); 3.598-3.593 (d, 1H, J=1.78); 3.360-3.355 (d, 1H, J=1.78); 3.27-3.22 (m, 2H). 13C NMR (DMSO-d6, 100 MHz): 170.69, 169.07, 165.69, 158.07, 158.04, 155.56, 155.53, 154.05, 153.31, 145.67, 136.62, 129.17, 128.48, 126.17, 116.17, 53.23, 52.93, 51.83, 34.67, 33.51. HRMS-ESI: m/z [M+H+] calculated for C19H16F2N6O5S: 479.4343, observed: m/z 479.0960 (M+H+): HPLC Method 2: Rt=17.32 min; 95.9%.

Workup

  1. extractionafter extraction

Sources & evidence

ORD record
ord-177e80eff3394a7ea599de9c96499365
Source dataset
uspto-grants-2016_08
Patent number
US09403843B2

Reaction notes

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