N,N'-Dimethylethylenediamine → 2-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-5-(4-(trifluoromethyl)-phenyl)pyridazin-3(2H)-one

HRID 2059876

Reaction equation

HRID 2059876 reaction equation
CNCCNC.[F:7][C:8]([F:23])([F:22])[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:20]=[N:19][NH:18][C:17](=[O:21])[CH:16]=2)=[CH:11][CH:10]=1.Br[C:25]1[CH:36]=[CH:35][C:28]([O:29][CH2:30][C:31]([CH3:34])([OH:33])[CH3:32])=[C:27]([O:37][CH3:38])[CH:26]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.C(Cl)Cl.[Cu]I>[OH:33][C:31]([CH3:34])([CH3:32])[CH2:30][O:29][C:28]1[CH:35]=[CH:36][C:25]([N:18]2[C:17](=[O:21])[CH:16]=[C:15]([C:12]3[CH:13]=[CH:14][C:9]([C:8]([F:7])([F:22])[F:23])=[CH:10][CH:11]=3)[CH:20]=[N:19]2)=[CH:26][C:27]=1[O:37][CH3:38]

Participants

8

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 62657Potassium Phosphate, TribasicHCID 579503875-(4-(Trifluoromethyl)phenyl)pyridazin-3(2H)-oneHCID 595950491-(4-Bromo-2-methoxyphenoxy)-2-methylpropan-2-ol

Product 1

HCID 469275062-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-5-(4-(trifluoromethyl)-phenyl)pyridazin-3(2H)-oneYield 41%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

N1,N2-dimethylethane-1,2-diamine (10 μL, 0.09 mmol) was added to a mixture of 5-(4-(trifluoromethyl)phenyl)pyridazin-3(2H)-one Part A (15 mg, 0.06 mmol), 1-(4-bromo-2-methoxyphenoxy)-2-methylpropan-2-ol Part B of Procedure 1 (20.6 mg, 0.08 mmol), potassium phosphate tribasic (39.8 mg, 0.19 mmol), and copper (I) iodide (17.8 mg, 0.09 mmol) in DMF (0.8 mL). After stirring at 110° C. overnight, the reaction mixture was diluted with CH2Cl2, filtered, washed with sat NaHCO3, brine, dried (MgSO4), and concentrated. The crude product was purified using HPLC (Phen Luna Axia C18 5μ 10:90:0.1 to 90:10:0.1 MeOH—H2O-TFA) to afford the desired product 2-(4-(2-hydroxy-2-methylpropoxy)-3-methoxyphenyl)-5-(4-(trifluoromethyl)-phenyl)pyridazin-3(2H)-one L-1 (11.7 mg, 0.03 mmol, 41.0% yield) as a yellow solid. LC/MS 435 (M+H)+, tR 0.94 min (method 5). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.20 (1H, d, J=2.01 Hz), 7.73-7.87 (4H, m), 7.17-7.26 (3H, m), 7.02 (1H, d, J=8.28 Hz), 3.91 (3H, s), 3.89 (2H, s), 1.38 (6H, s)

Workup

  1. filtrationfiltered
  2. washwashed
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customThe crude product was purified

Sources & evidence

ORD record
ord-bd05582678e547a0bfefcd9ecddf21a2
Source dataset
uspto-grants-2012_10
Patent number
US08278316B2

Linked notes

Loading…