Ammonium Chloride → Methyl 4-[(6-morpholin-4-yl-pyridazin-3-ylamino)-methyl]-benzoate

HRID 852919ノート

反応式

HRID 852919 の反応式
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl.[NH2:15][CH2:16][C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][CH:18]=1.[NH4+].[Cl-]>CC(O)C>[N:8]1([C:5]2[N:6]=[N:7][C:2]([NH:15][CH2:16][C:17]3[CH:18]=[CH:19][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:25][CH:26]=3)=[CH:3][CH:4]=2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1

参加物

5

反応物 3

HCID 25517Ammonium ChlorideHCID 3210794-(6-Chloropyridazin-3-yl)morpholineHCID 2729253Methyl 4-(aminomethyl)benzoate hydrochloride

生成物 1

HCID 58930537Methyl 4-[(6-morpholin-4-yl-pyridazin-3-ylamino)-methyl]-benzoate収率 8.2%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
150 °C

実験手順

To a solution of 64 (2.0 g, 10.0 mmol) and methyl 4-(aminomethyl)benzoate hydrochloride (2.2 g, 11.0 mmol) in i-PrOH (200 mL) was added NH4Cl (2.14 g, 40.0 mmol). The reaction mixture was heated at 150° C. for 72 h and concentrated. The residue was dissolved in water and the aqueous phase was extracted with. \the aqueous phase was separated, treated with 1N NaOH (pH 8) and extracted with EtOAc. The extract was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (MeOH/CH2Cl2: 2/98 to 5/95) to afford the title compound 65 (270 mg, 0.82 mmol, 8% yield). 1H NMR: (400 MHz, CDCl3) δ (ppm): 7.97 (d, J=8.0 Hz, 2H), 7.42 (d, J=8.0 Hz, 2H), 6.90 (d, J=9.2 Hz, 1H), 6.69 (d, J=9.2 Hz, 1H), 5.16-5.06 (bs, 1H), 4.67 (s, 2H), 3.90 (s, 3H), 3.82 (t, J=4.8 Hz, 4H), 3.41 (t, J=4.8 Hz, 4H).

後処理

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in water
  3. extractionthe aqueous phase was extracted with
  4. custom\the aqueous phase was separated
  5. additiontreated with 1N NaOH (pH 8)
  6. extractionextracted with EtOAc
  7. dry with materialThe extract was dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography on silica gel (MeOH/CH2Cl2: 2/98 to 5/95)

出典と根拠

ORDレコード
ord-89f41a02d34945428ae3af8a28b1dab5
出典データセット
uspto-grants-2007_08
特許番号
US07253204B2

反応ノート

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