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

反応式

HRID 877354 の反応式
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]

参加物

10

反応物 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric Acid2 回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

生成物 1

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

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 3283Diethyl Ether溶媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-9bc49c3e909644918539c59a87a8e2e9
出典データセット
uspto-grants-2015_03
特許番号
US08987310B2

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