1,2-Dichloroethane → 2-(4-isopropylphenyl)-N-{(S)-(1-methyl-1H-1,2,3-triazol-4-yl)[4-(2,2,2-trifluoroethoxy)-phenyl]methyl}acetamide

HRID 877354

Reaction equation

HRID 877354 reaction equation
CC(S([NH:7][C@H:8]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]([F:30])([F:29])[F:28])=[CH:21]N=1)[C:9]1[N:10]=[N:11][N:12]([CH2:14][Si](C)(C)C)[CH:13]=1)=O)(C)C.Cl.[CH:32]([C:35]1[CH:40]=[CH:39][C:38]([CH2:41][C:42]([OH:44])=O)=[CH:37][CH:36]=1)([CH3:34])[CH3:33].[CH:45]1C=NC2N(O)N=NC=2C=1.C(Cl)CCl.C(N(C(C)C)CC)(C)C>CO.CCOCC.C(Cl)Cl>[CH:32]([C:35]1[CH:40]=[CH:39][C:38]([CH2:41][C:42]([NH:7][C@H:8]([C:9]2[N:10]=[N:11][N:12]([CH3:14])[CH:13]=2)[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][C:27]([F:28])([F:29])[F:30])=[CH:21][CH:45]=2)=[O:44])=[CH:37][CH:36]=1)([CH3:34])[CH3:33]

Participants

10

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric Acid2×HCID 782304-Isopropylphenylacetic acidHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 1317325962-methyl-N-[(S)-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]{1-[(trimethylsilyl)methyl]-1H-1,2,3-triazol-4-yl}methyl]propane-2-sulfinamide

Product 1

HCID 529320512-(4-isopropylphenyl)-N-{(S)-(1-methyl-1H-1,2,3-triazol-4-yl)[4-(2,2,2-trifluoroethoxy)-phenyl]methyl}acetamide

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-methyl-N-[(S)-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]{1-[(trimethylsilyl)methyl]-1H-1,2,3-triazol-4-yl}methyl]propane-2-sulfinamide (1.3 g, 2.8 mmol) in MeOH (6.3 mL) was added a solution of HCl in ether (6.3 mL, 2 M). The reaction was stirred at room temperature for 1 h. The solvents were removed by concentration. The resulted amine bis-HCl salt (0.3 g, 0.69 mmol) was mixed with 4-isopropylpheylacetic acid (0.12 g, 0.69 mmol), HOAt (0.094 g, 0.69 mmol), EDC (0.13 g, 0.69 mmol) and diisopropylethyl amine (0.23 mL, 1.4 mmol) in CH2Cl2 (3.5 mL) and stirred at room temperature for 0.5 h. The solvent was removed and the residue was purified by silica gel flash chromatography (30-100% EtOAc in Hex) to give the amide product. To a solution of this amide (0.23 g, 0.45 mmol) in THF (3 mL) was added a solution of TBAF (0.5 mL, 1M in THF). The reaction mixture was stirred at rt for 1 h. The solvent was removed and the residue was purified by silica gel flash chromatography (50-100% EtOAc in hex) to provide 2-(4-isopropylphenyl)-N-{(S)-1-methyl-1H-1,2,3-triazol-4-yl)[4-(2,2,2-trifluoroethoxy)-phenyl]methyl}acetamide (0.12 g, 59%). 1H NMR (CDCl3, 400 MHz) δ 8.22 (d, J=2.8 Hz, 1H), 7.40 (s, 1H), 7.39 (d, J=7.2 Hz, 1H), 7.33 (d, J=8.8 Hz, 1H), 7.24-7.19 (m, 5H), 6.27 (d, J=6.8 Hz, 1H), 4.31 (dd, J=7.6, 8.4 Hz, 2H), 4.00 (s, 3H), 3.62 (s, 2H), 2.90 (m, J=6.8 Hz, 1H), 1.25 (d, J=6.8 Hz, 6H). HRMS (ES) [M+1]+ calcd for C22H24F3N5O2: 448.1955, Found: 448.1956.

Workup

  1. customThe solvents were removed by concentration
  2. stirringstirred at room temperature for 0.5 h
  3. customThe solvent was removed
  4. customthe residue was purified by silica gel flash chromatography (30-100% EtOAc in Hex)

Sources & evidence

ORD record
ord-9bc49c3e909644918539c59a87a8e2e9
Source dataset
uspto-grants-2015_03
Patent number
US08987310B2

Linked notes

Loading…