Trimethylsilyldiazomethane → methyl 2-(4-{(S)-[(tert-butylsulfinyl)amino][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)-2-methylpropanoate

HRID 877358Notes

Reaction equation

HRID 877358 reaction equation
[C:1]([S:5]([NH:7][C@H:8]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]([F:31])([F:30])[F:29])=[CH:22][N:21]=1)[C:9]1[N:10]=[N:11][N:12]([C:14]([CH3:19])([CH3:18])[C:15]([OH:17])=[O:16])[CH:13]=1)=[O:6])([CH3:4])([CH3:3])[CH3:2].[Si](C=[N+]=[N-])(C)(C)[CH3:33]>C1(C)C=CC=CC=1.CO>[C:1]([S:5]([NH:7][C@H:8]([C:20]1[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]([F:30])([F:29])[F:31])=[CH:22][N:21]=1)[C:9]1[N:10]=[N:11][N:12]([C:14]([CH3:19])([CH3:18])[C:15]([O:17][CH3:33])=[O:16])[CH:13]=1)=[O:6])([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 2

HCID 167693TrimethylsilyldiazomethaneHCID 681578412-(4-{(S)-[(tert-butylsulfinyl)amino][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)-2-methylpropanoic acid

Product 1

HCID 67174474methyl 2-(4-{(S)-[(tert-butylsulfinyl)amino][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)-2-methylpropanoateYield 38.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Procedure

To a solution of 0.30 g (0.65 mmol) 2-(4-{(S)-[(tert-butylsulfinyl)amino][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)-2-methylpropanoic acid in 2.5 ml toluene and 0.81 ml MeOH at rt was added 1.3 ml (2.6 mmol) 2.0 M TMS-diazomethane in hexanes. After 4 h at room temperature, the reaction mixture was concentrated in vacuo. Purification by flash chromatography (silica gel, linear gradient 0-15% MeOH in CH2Cl2) afforded 0.12 g (38%) methyl 2-(4-{(S)-[(tert-butylsulfinyl)amino][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}-1H-1,2,3-triazol-1-yl)-2-methylpropanoate. ES-MS [M+1]+=478.2. 1H NMR (CDCl3, 400 MHz) δ 8.29 (d, J=2.75 Hz, 1H), 7.59 (s, 1H), 7.48 (d, J=8.70 Hz, 1H), 7.24 (m, 1H); 5.87 (d, J=5.31 Hz, 1H,), 5.33 (d, J=5.31 Hz, 1H), 4.38 (q, J=7.70, 2H), 3.71 (d, J=0.82 Hz, 1H); 1.92 (d, J=1.65 Hz, 6H); 1.27 (s, 9H).

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. customPurification by flash chromatography (silica gel, linear gradient 0-15% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-2dd564f160dc4c9ca996757cab284182
Source dataset
uspto-grants-2015_03
Patent number
US08987310B2

Reaction notes

Loading…