1-Azido-3,5-bis(trifluoromethyl)benzene → (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

HRID 1478643Notes

Reaction equation

HRID 1478643 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]1[C@@H:8]([C:9](=[O:24])[NH:10][C@@H:11]([CH2:18][C:19]2[N:20]=[CH:21][S:22][CH:23]=2)[C:12](=[O:17])[NH:13][CH2:14][C:15]#[CH:16])[O:7]1)=[O:5])[CH3:2].[N:25]([C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=1)=[N+:26]=[N-:27].CCCC[Sn](OC(C)=O)(CCCC)CCCC>CC(O)(C)C.CCO.O.CN(C=O)C.[O-]S([O-])(=O)=O.[Cu+2]>[CH2:1]([O:3][C:4]([C@@H:6]1[C@@H:8]([C:9](=[O:24])[NH:10][C@@H:11]([CH2:18][C:19]2[N:20]=[CH:21][S:22][CH:23]=2)[C:12]([NH:13][CH2:14][C:15]2[N:27]=[N:26][N:25]([C:28]3[CH:29]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:31]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:33]=3)[CH:16]=2)=[O:17])[O:7]1)=[O:5])[CH3:2]

Participants

7

Reactant 3

HCID 131060951-Azido-3,5-bis(trifluoromethyl)benzeneHCID 16682741Tributyltin acetateHCID 71817782(2S,3S)-ethyl-3-((S)-1-oxo-1-(prop-2-ynylamino)-3-(thiazol-4-yl)propan-2-ylcarbamoyl)oxirane-2-carboxylate

Product 1

HCID 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-carboxylateYield 87.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 24462Copper SulfateCatalystHCID 86659795HCID 86659795, compoundSolvent

Procedure

The general click procedure was used substituting the following quantities using: 37 (93.7 mg, 0.27 mmol); 1-azido-3,5-bis(trifluoromethyl)benzene (82.5 mg, 0.32 mmol); CuSO4 (0.6 mg, 0.01 mmol); NaAsc (3.5 mg, 0.02 mmol); TBTA (15.0 mg, 0.03 mmol); in t-BuOH/EtOH/H2O (4:4:2) with an additional 3 drops of DMF; afforded the 43 as a while solid (142 mg, 87.8%). 1H NMR (CDCl3, 400 MHz): δ 8.77 (s, 1H); 8.25 (s, 2H); 8.09 (s, 1H): 7.96 (s, 1H); 7.77-7.75 (d, 1H, J=7.09 Hz); 7.34-7.32 (t, 1H); 7.11 (s, 1H); 4.81-4.76 (q, 1H); 4.59-4.57 (d, 2H, J=5.90 Hz); 4.31-4.25 (m, 2H); 3.72-3.711 (d, 1H, J=1.64 Hz); 3.55-3.54 (d, 1H, J=1.64 Hz); 3.41-3.17 (m, 2H); 1.01-0.99 (t, 3H). 13C NMR (DMSO-d6, 100 MHz): 170.62, 167.49, 165.37, 154.06, 153.24, 146.92, 138.31, 124.57, 122.37, 121.85, 121.09, 116.21, 61.97, 53.44, 52.97, 51.74, 34.64, 33.49, 14.29.

Sources & evidence

ORD record
ord-32520ed271ee44b89c48cfda50ff59e4
Source dataset
uspto-grants-2016_08
Patent number
US09403843B2

Reaction notes

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