Sodium Chloride → (6-Chloro-5-isopropyl-pyridazin-3-yl)-[2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile

HRID 271194Notes

Reaction equation

HRID 271194 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([CH2:8][O:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][O:11]2)[CH:5]=[C:4]([Br:16])[C:3]=1[CH2:17][C:18]#[N:19].[H-].[Na+].[Cl:22][C:23]1[N:24]=[N:25][C:26](Cl)=[CH:27][C:28]=1[CH:29]([CH3:31])[CH3:30].[Cl-].[Na+].C(=O)(O)[O-].[Na+]>CN(C)C=O.O>[Cl:22][C:23]1[N:24]=[N:25][C:26]([CH:17]([C:3]2[C:2]([Br:1])=[CH:7][C:6]([CH2:8][O:9][CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][O:11]3)=[CH:5][C:4]=2[Br:16])[C:18]#[N:19])=[CH:27][C:28]=1[CH:29]([CH3:31])[CH3:30]

Participants

8

Reactant 5

HCID 5234Sodium ChlorideHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 140241623,6-Dichloro-4-isopropylpyridazineHCID 59834537[2,6-Dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile

Product 1

HCID 59834544(6-Chloro-5-isopropyl-pyridazin-3-yl)-[2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrileYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
25 °C

Procedure

A solution of [2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile (60) (1.52 g, 3.91 mmol) in N,N-dimethylformamide (9 mL) at 25° C. was treated with sodium hydride (192.8 mg, 4.82 mmol, 60% dispersion in mineral oil). The reaction mixture was stirred at 25° C. for 10 min. At this time, the reaction was treated with a solution of 3,6-dichloro-4-isopropyl-pyridazine (7) (810 mg, 4.24 mmol) in N,N-dimethylformamide (2 mL). The reaction was then heated to 90° C. for 1 h. At this time, the reaction was cooled to 25° C., diluted with water (50 mL), a saturated aqueous sodium chloride solution (50 mL) and a saturated aqueous sodium bicarbonate solution (20 mL). This mixture was extracted with ethyl acetate (200 mL). The organics were washed with a saturated aqueous sodium chloride solution (100 mL), dried with magnesium sulfate, filtered, and concentrated under vacuum. Isco chromatography (120 g, Silica, 2:1 hexanes/ethyl acetate) afforded (6-chloro-5-isopropyl-pyridazin-3-yl)-[2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile (61) (964 mg, 65%) as an orange viscous oil; LRMS for C21H22Br2ClN3O2 (M+H) at m/z=542. Molecular Weight=543.6894; Exact Mass=540.9767

Workup

  1. temperatureThe reaction was then heated to 90° C. for 1 h
  2. temperatureAt this time, the reaction was cooled to 25° C.
  3. extractionThis mixture was extracted with ethyl acetate (200 mL)
  4. washThe organics were washed with a saturated aqueous sodium chloride solution (100 mL)
  5. dry with materialdried with magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-55ebe323b03c44efa3f44e4285b50e55
Source dataset
uspto-grants-2008_11
Patent number
US07452882B2

Reaction notes

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