Lithium Hydroxide → Calpain inhibitor-1

HRID 1478649Notes

Reaction equation

HRID 1478649 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]([F:27])=[CH:23][CH:22]=3)[CH:20]=2)=[O:13])[O:7]1)=[O:5])C.[Li+].[OH-]>>[F: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 117863624(2S,3S)-ethyl-3-((S)-1-((1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)methylamino)-1-oxo-3-(thiazol-4-yl)propan-2-ylcarbamoyl)oxirane-2-carboxylate

Product 1

HCID 71660816Calpain inhibitor-1Yield 76.2%

Procedure

Followed general procedure using: the corresponding peptidomimetic epoxide ethyl ester 39 (25 mg, 0.51 mmol); LiOH (1.3 mg, 0.06 mmol); after extraction afforded the desired product as a white solid (18 mg, 76.2%). 1H NMR (DMSO-d6, 400 MHz): δ 8.98 (s, 1H); 8.72-8.70 (t, 1H); 8.57-8.55 (d, 1H, J=8.06); 8.48 (s, 1H); 7.93-7.90 (q, 2H); 7.48-7.44 (t, 2H); 7.34 (s, 1H); 4.70-4.65 (q, 1H); 4.40-4.38 (d, 2H; J=5.52); 3.66 (s, 1H); 3.54-3.06 (m, 3H). 13C NMR (DMSO-d6, 100 MHz): 170.62, 165.75, 163.24, 160.80, 154.06, 153.32, 146.40, 133.62, 122.81, 122.72, 121.76, 117.33, 117.10, 53.24, 53.01, 52.94, 34.77, 33.50. HRMS-ESI: m/z [M+H+] calculated for C19H17FN6O5S: 461.1043, observed: m/z 461.1049 (M+H+): HPLC Method 2: Rt=17.9 min; purity=97.2%.

Workup

  1. extractionafter extraction

Sources & evidence

ORD record
ord-056f8cd4de4e4bd4a30c99fa9d66e772
Source dataset
uspto-grants-2016_08
Patent number
US09403843B2

Reaction notes

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