Potassium Carbonate → 5-(5-Fluoro-pyridin-2-ylmethoxy)-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one

HRID 469683

反応式

HRID 469683 の反応式
[OH:1][C:2]1[CH:7]=[N:6][N:5]([CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][O:9]2)[C:4](=[O:14])[CH:3]=1.Br[CH2:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][N:18]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(Cl)Cl>[F:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][O:1][C:2]2[CH:7]=[N:6][N:5]([CH:8]3[CH2:13][CH2:12][CH2:11][CH2:10][O:9]3)[C:4](=[O:14])[CH:3]=2)=[N:18][CH:19]=1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 247293132-(Bromomethyl)-5-fluoropyridineHCID 579503555-Hydroxy-2-(2-tetrahydropyranyl)pyridazin-3(2H)-one

生成物 1

HCID 580921945-(5-Fluoro-pyridin-2-ylmethoxy)-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one収率 27%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

5-Hydroxy-2-(tetrahydro-2H-pyran-2-yl)pyridazin-3(2H)-one (2.62 g, 13.4 mmol) (this compound was prepared in accordance with the procedure of Stenkamp et al., WO 2008022979), 2-(bromomethyl)-5-fluoropyridine (7.6 g, 40.2 mmol) and K2CO3 (9.24 g, 67 mmol) were stirred in DMF (40 ml) and CH2Cl2 (40 ml) for 48 h. The mixture was diluted with CH2Cl2, washed with 5% LiCl solution (4×) and concentrated. The residue was purified by column chromatography (40 g ISCO column column eluting with methylene chloride and a 10:1 methanol/ammonium hydroxide mixture; gradient 100% methylene chloride to 95% methylene chloride) to yield the title compound (1.1 g, 27%) as a light brown solid: 1H NMR (300 MHz, CDCl3) δ 8.47 (s, 1H), 7.73 (d, J=2.9 Hz, 1H), 7.47-7.43 (m, 2H), 6.19 (d, J=2.9 Hz, 1H), 6.03-5.98 (dd, J=10.7, 2.0 Hz, 1H), 5.12 (s, 2H), 4.18-4.08 (m, 1H), 3.78-3.69 (td, J=11.6, 2.6 Hz, 1H), 2.21-2.00 (m, 2H), 1.75-1.60 (m, 4H).

後処理

  1. washwashed with 5% LiCl solution (4×)
  2. concentrationconcentrated
  3. customThe residue was purified by column chromatography (40 g ISCO column column
  4. washeluting with methylene chloride

出典と根拠

ORDレコード
ord-7847f30b0978442da88963b284232b89
出典データセット
uspto-grants-2014_01
特許番号
US08629158B2

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