Potassium Carbonate → 2-(Tetrahydro-2H-pyran-2-yl)-5-((6-(trifluoromethyl)pyridin-3-yl)methoxy)pyridazin-3(2H)-one

HRID 474934

반응식

HRID 474934 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:18]=[CH:19][C:20]([C:23]([F:26])([F:25])[F:24])=[N:21][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(Cl)Cl>[O:9]1[CH2:10][CH2:11][CH2:12][CH2:13][CH:8]1[N:5]1[C:4](=[O:14])[CH:3]=[C:2]([O:1][CH2:16][C:17]2[CH:22]=[N:21][C:20]([C:23]([F:26])([F:24])[F:25])=[CH:19][CH:18]=2)[CH:7]=[N:6]1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 144051255-(Bromomethyl)-2-(trifluoromethyl)pyridineHCID 579503555-Hydroxy-2-(2-tetrahydropyranyl)pyridazin-3(2H)-one

생성물 1

HCID 668688942-(Tetrahydro-2H-pyran-2-yl)-5-((6-(trifluoromethyl)pyridin-3-yl)methoxy)pyridazin-3(2H)-one수율 123.1%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매2회

실험 절차

5-Hydroxy-2-(tetrahydro-2H-pyran-2-yl)pyridazin-3(2H)-one (2.3 g, 12 mmol), 5-(bromomethyl)-2-(trifluoromethyl)pyridine (7.2 g, 30 mmol) and K2CO3 (8.4 g, 60 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 (5.25 g, >100%) as a waxy white solid containing some DMF: 1H NMR (300 MHz, CDCl3) δ 8.78 (d, J=1.8 Hz, 1H), 7.97-7.88 (m, 1H), 7.76 (d, J=7.9 Hz, 1H), 7.72 (m, 1H), 6.20 (d, J=2.9 Hz, 1H), 6.03-5.98 (d, J=10.9, 2.0 Hz, 1H), 5.11 (s, 2H), 4.16-4.08 (m, 1H), 3.79-3.69 (m, 1H), 2.24-1.96 (m, 2H), 1.83-1.48 (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-04101919e5954239b255875565c24114
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637501B2

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