Perfluoro-1-butanesulfonyl fluoride → 2-(4-tert-Butylphenyl)-N-{(S)-[1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}acetamide

HRID 877385Notes

Reaction equation

HRID 877385 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([NH:14][C@@H:15]([C:28]2[N:29]=[N:30][N:31]([CH2:33][CH2:34]O)[CH:32]=2)[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]([F:27])([F:26])[F:25])=[CH:18][N:17]=2)=[O:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.[F:45]C(F)(S(F)(=O)=O)C(F)(F)C(F)(F)C(F)(F)F>CC#N.O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([NH:14][C@@H:15]([C:28]2[N:29]=[N:30][N:31]([CH2:33][CH2:34][F:45])[CH:32]=2)[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][C:24]([F:26])([F:25])[F:27])=[CH:18][N:17]=2)=[O:13])=[CH:7][CH:6]=1)([CH3:2])([CH3:4])[CH3:3]

Participants

6

Reactant 3

HCID 67814Perfluoro-1-butanesulfonyl fluorideHCID 81531DiisopropylethylamineHCID 681568672-(4-tert-Butylphenyl)-N-{(S)-[1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}acetamide

Product 1

HCID 681564552-(4-tert-Butylphenyl)-N-{(S)-[1-(2-fluoroethyl)-1H-1,2,3-triazol-4-yl][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}acetamideYield 53.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-(4-tert-Butylphenyl)-N-{(S)-[1-(2-hydroxyethyl)-1H-1,2,3-triazol-4-yl][5-(2,2,2-trifluoroethoxy)pyridin-2-yl]methyl}acetamide (32.00 mg, 0.0650 mmol) in 0.5 ml of anhydrous CH3CN at RT was added diisopropylethylamine (0.0450 ml, 0.260 mmol), diisopropylethylamine dihydrogen fluoride complex (0.0180 ml, 0.0980 mmol), and perfluorobutanesulfonyl fluoride (0.0230 ml, 0.130 mmol). The resulting solution was stirred at room temperature for 16 hours. The reaction mixture was diluted with water and extracted with CH2Cl2. The combined organic layers were washed with brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuum. Purification by preparative HPLC (20-90% CH3CN/H2O over 30 min, 0.05% added TFA, C18 column) to afford 0.0171 g (53%) of the title compound. 1H NMR (CDCl3, 400 MHz) δ 8.245 (d, J=2.93 Hz, 1H), 7.569 (s, 1H), 7.527 (d, J=7.14 Hz, 1H), 7.369 (m, 2H), 7.270 (m, 1H), 7.225 (m, 2H), 6.336 (d, J=7.14 Hz, 1H), 4.800 (AB q, J=4.53 Hz, 1H), 4.682 (AB q, J=4.21 Hz, 1H), 4.617 (AB q, J=4.53 Hz, 1H), 4.550 (AB q, J=4.67 Hz, 1H), 4.378 (q, J=7.88 Hz, 2H), 3.623 (s, 2H), 3.086 (br s, 1H), 1.314 (s, 9H). ES-MS [M+1]+: 494.2.

Workup

  1. extractionextracted with CH2Cl2
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuum
  6. customPurification
  7. additionby preparative HPLC (20-90% CH3CN/H2O over 30 min, 0.05% added TFA, C18 column)

Sources & evidence

ORD record
ord-caf37a2a62464f4fa0a856d51c9e73d5
Source dataset
uspto-grants-2015_03
Patent number
US08987310B2

Reaction notes

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