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

반응식

HRID 877354 반응식
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]

참가 물질

10

반응물 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric Acid2회HCID 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

생성물 1

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

시약·촉매·용매 3

HCID 887Methanol용매HCID 3283Diethyl Ether용매HCID 6344Dichloromethane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-9bc49c3e909644918539c59a87a8e2e9
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08987310B2

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