Triethylamine → 4-(3-(3-methylpyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamide

HRID 1666401ノート

反応式

HRID 1666401 の反応式
Cl.[CH3:2][C:3]1[C:4]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([CH:16]=[C:17]3[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]3)[CH:11]=2)=[N:5][CH:6]=[CH:7][CH:8]=1.[N:23]1[CH:28]=[CH:27][CH:26]=[C:25]([NH:29][C:30](=O)[O:31]C2C=CC=CC=2)[N:24]=1.C(N(CC)CC)C>C(#N)C>[CH3:2][C:3]1[C:4]([O:9][C:10]2[CH:11]=[C:12]([CH:13]=[CH:14][CH:15]=2)[CH:16]=[C:17]2[CH2:22][CH2:21][N:20]([C:30]([NH:29][C:25]3[N:24]=[N:23][CH:28]=[CH:27][CH:26]=3)=[O:31])[CH2:19][CH2:18]2)=[N:5][CH:6]=[CH:7][CH:8]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 20150036Phenyl pyridazin-3-ylcarbamateHCID 668760903-Methyl-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine hydrochloride

生成物 1

HCID 249644244-(3-(3-methylpyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamide収率 66.7%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

3-Methyl-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine hydrochloride (500 mg, 1.42 mmol, from Example 42, Step 5), phenyl pyridazin-3-ylcarbamate (335 mg, 1.56 mmol) and triethylamine (0.79 mL, 5.66 mmol) were combined in acetonitrile (10 mL) and stirred at room temperature. After 16 h, the reaction was concentrated forming a residue and the residue was partitioned between EtOAc and water. The organic layer was separated, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (0-5%, (8:1 EtOH:conc. NH4CH):CH2Cl2) to afford the title compound (380 mg) as a white foam. MS (APCI 10V) AP+ 402.0, 281.1; 1H NMR (400 MHz, CD3OD) δ ppm 2.33 (s, 3H) 2.46 (td, J=5.86, 0.80 Hz, 2H) 2.59 (td, J=5.71, 0.82 Hz, 2H) 3.52-3.62 (m, 2H) 3.64-3.71 (m, 2H) 6.44 (s, 1H) 6.84-6.94 (m, 2H) 7.03 (d, J=7.24 Hz, 1H) 7.05 (d, J=7.33 Hz, 1H) 7.34 (dd, J=8.78, 7.66 Hz, 1H) 7.59 (dd, J=9.15, 4.67 Hz, 1H) 7.66-7.73 (m, 1H) 7.87-7.96 (m, J=4.96, 1.22, 0.55, 0.55 Hz, 1H) 8.12 (d, J=8.97 Hz, 1H) 8.78 (d, J=4.26 Hz, 1H).

後処理

  1. concentrationthe reaction was concentrated
  2. customforming a residue
  3. customthe residue was partitioned between EtOAc and water
  4. customThe organic layer was separated
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (0-5%, (8:1 EtOH:conc. NH4CH):CH2Cl2)

出典と根拠

ORDレコード
ord-6c706a13c73343d6a36cebd4dac56402
出典データセット
uspto-grants-2011_10
特許番号
US08044052B2

反応ノート

読み込み中…