Diisopropylethylamine → 6-(2-Chlorophenyl)-7-(4-chlorophenyl)-3-(cyclohexylmethyl)-[1,2,4]triazolo[4,3-b]pyridazine

HRID 2266310ノート

反応式

HRID 2266310 の反応式
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]=[N:12][C:11]([NH:14][NH:15][C:16](=O)[CH2:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)=[CH:10][C:9]=1[C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1.C(N(C(C)C)CC)(C)C.[Cl-].[Cl-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([C:25]2[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=2)=[CH:10][C:11]2[N:12]([C:16]([CH2:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)=[N:15][N:14]=2)[N:13]=1

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 13797396Triphenylphosphane dichlorideHCID 57979752N'-(6-(2-chlorophenyl)-5-(4-chlorophenyl)pyridazin-3-yl)-2-cyclohexylacetohydrazide

生成物 1

HCID 119931086-(2-Chlorophenyl)-7-(4-chlorophenyl)-3-(cyclohexylmethyl)-[1,2,4]triazolo[4,3-b]pyridazine収率 102.9%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a suspension of N′-(6-(2-chlorophenyl)-5-(4-chlorophenyl)pyridazin-3-yl)-2-cyclohexylacetohydrazide (46 mg, 0.1 mmol) in THF (2 mL) at room temperature was added diisopropylethylamine (0.14 mL, 0.8 mmol). After 5 min, triphenylphosphine dichloride (110 mg, 0.33 mmol) was added, and the reaction mixture stirred at room temperature for 16 h. Analysis by HPLC/MS indicated the reaction was complete. The reaction was diluted with EtOAc (40 mL), washed with H2O, saturated aqueous NaCl, dried (Na2SO4), filtered and concentrated. The obtained residue was purified using a silica gel cartridge (12 g) eluting with a gradient of EtOAc (0-30%) in hexanes to yield 45 mg of the desired product with 80% purity (contaminated with triphenylphosphine oxide). The product was further purified using reverse phase preparative HPLC (Conditions: Phenomenex Luna 5μ C18 21.2×100 mm; Eluted with 70% to 100% B, 8 min gradient, 100% B hold for 7 min, (A 90% H2O, 10% MeOH and B=10% H2O, 90% MeOH); Flow rate at 20 mL/min, UV detection at 220 nm) to afford 30 mg (68%) of the title compound as a white powder. HPLC/S (method A): retention time=4.22 min, (M+H)+=437.1. 1H NMR (CDCl3, 400 MHz): δ 8.03 (s, 1H), 7.33-7741 (m, 4H), 7.21-7.28 (m, 2H), 7.07 (d, J=8.31 Hz, 2H), 3.14 (d, J=7.09 Hz, 2H), 2.01-2.12 (m, 1H), 1.69-1.80 (m, 4H), 1.21-1.29 (m, 3H), 1.10-1.17 (m, 3H).

後処理

  1. washwashed with H2O, saturated aqueous NaCl
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe obtained residue was purified
  6. washeluting with a gradient of EtOAc (0-30%) in hexanes

出典と根拠

ORDレコード
ord-0e0ff5fef1b34e948028926898101deb
出典データセット
uspto-grants-2010_12
特許番号
US07858639B2

反応ノート

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