Lithium Hydroxide → (2S,3S)-3-((S)-1-((1-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methylamino)-1-oxo-3-(thiazol-4-yl)propan-2-ylcarbamoyl)oxirane-2-carboxylic acid

HRID 1478652Notes

Reaction equation

HRID 1478652 reaction equation
C([O:3][C:4]([C@@H:6]1[C@@H:8]([C:9](=[O:41])[NH:10][C@@H:11]([CH2:35][C:36]2[N:37]=[CH:38][S:39][CH:40]=2)[C:12]([NH:14][CH2:15][C:16]2[N:17]=[N:18][N:19]([C:21]3[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:22]=3)[CH:20]=2)=[O:13])[O:7]1)=[O:5])C.[Li+].[OH-]>>[F:30][C:27]([F:28])([F:29])[C:25]1[CH:26]=[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:41])[CH2:35][C:36]3[N:37]=[CH:38][S:39][CH:40]=3)[N:17]=[N:18]2)[CH:22]=[C:23]([C:31]([F:34])([F:33])[F:32])[CH:24]=1

Participants

3

Reactant 2

HCID 3939Lithium HydroxideHCID 131736514(2S,3S)-ethyl-3-((S)-1-((1-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methylamino)-1-oxo-3-(thiazol-4-yl)propan-2-ylcarbamoyl)oxirane-2-carboxylate

Product 1

HCID 71818084(2S,3S)-3-((S)-1-((1-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,3-triazol-4-yl)methylamino)-1-oxo-3-(thiazol-4-yl)propan-2-ylcarbamoyl)oxirane-2-carboxylic acidYield 83%

Procedure

Followed general procedure using: the corresponding peptidomimetic epoxide ethyl ester 43 (94 mg, 0.15 mmol); LiOH (3.7 mg, 0.15 mmol); after extraction afforded the desired product as a white solid (72 mg, 80.3%). 1H NMR (DMSO-d6, 400 MHz): δ 8.99-8.98 (d, 1H, J=1.92 Hz); 8.92 (s, 1H); 8.79-8.77 (t, 1H); 8.63 (s, 2H); 8.57-8.55 (d, 1H, J=8.27 Hz); 8.27 (s, 1H); 7.34-7.33 (d, 1H, J=1.85 Hz); 4.71-4.66 (m, 1H); 4.43-4.42 (d, 2H, J 5.67 Hz); 3.58-3.57 (d, 1H, J=1.73 Hz); 3.36-3.35 (d, 1H, J=1.70 Hz); 3.28-3.10 (m, 2H). 13C NMR (DMSO-d6, 100 MHz): 170.67, 169.07, 165.80, 154.06, 153.29, 146.93, 138.32, 132.48, 132.14, 122.38, 121.11, 116.18, 53.22, 52.90, 51.96, 34.64, 33.51. HRMS-ESI: m/z [M+H+] calculated for C21H16F6N6O5S: 579.4443, observed: m/z 579.0890 (M+H+); m/z 577.0775 (M+H+). HPLC method 2: Rt=24.5 min; purity=95.3%.

Workup

  1. extractionafter extraction

Sources & evidence

ORD record
ord-a01b884b71564bd6bb76406520cc0e2d
Source dataset
uspto-grants-2016_08
Patent number
US09403843B2

Reaction notes

Loading…