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

HRID 469683

Reaction equation

HRID 469683 reaction equation
[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

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-7847f30b0978442da88963b284232b89
Source dataset
uspto-grants-2014_01
Patent number
US08629158B2

Linked notes

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