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

HRID 469683

반응식

HRID 469683 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-7847f30b0978442da88963b284232b89
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08629158B2

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