Triethylamine → 4-(3-(6-methylpyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamide

HRID 1666394ノート

反応式

HRID 1666394 の反応式
Cl.[CH3:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([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:4]=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[N:4]=[C:5]([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)[CH:6]=[CH:7][CH:8]=1

参加物

5

反応物 3

HCID 8471TriethylamineHCID 20150036Phenyl pyridazin-3-ylcarbamateHCID 668757912-Methyl-6-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine hydrochloride

生成物 1

HCID 249640624-(3-(6-methylpyridin-2-yloxy)benzylidene)-N-(pyridazin-3-yl)piperidine-1-carboxamide収率 58.9%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

2-Methyl-6-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine hydrochloride (500 mg, 1.42 mmol, from Example 40, 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. NH4OH):CH2Cl2) to afford the title compound (336 mg) as a foamy white solid. MS (APCI 10V) AP+ 402.0, 281.1; 1H NMR (400 MHz, CD3OD) δ ppm 2.42 (s, 3H) 2.46 (td, J=5.84, 0.80 Hz, 2H) 2.58 (td, J=5.78, 1.13 Hz, 2H) 3.52-3.63 (m, 2H) 3.63-3.72 (m, 2H) 6.45 (s, 1H) 6.65 (dt, J=8.21, 0.69 Hz, 1H) 6.90-6.97 (m, 2H) 6.99 (dt, J=7.16, 0.48 Hz, 1H) 7.04-7.11 (m, J=8.10, 1.21, 0.84, 0.63 Hz, 1H) 7.36 (dd, J=8.86, 7.71 Hz, 1H) 7.59 (dd, J=9.11, 4.65 Hz, 1H) 7.68 (dd, J=8.08, 7.52 Hz, 1H) 8.12 (d, J=8.87 Hz, 1H) 8.79 (d, J=3.90 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. NH4OH):CH2Cl2)

出典と根拠

ORDレコード
ord-c166c5fe030a4079901e7f41dabd23d6
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…