Sodium hydride → HCID 10459001, compound

HRID 2055954Notes

Reaction equation

HRID 2055954 reaction equation
Cl[C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1.[OH:19][C:20]1[CH:29]=[CH:28][CH:27]=[C:26]2[C:21]=1[CH:22]=[CH:23][N:24]=[CH:25]2.[H-].[Na+]>CN(C=O)C>[CH:25]1[C:26]2[C:21](=[C:20]([O:19][C:5]3[N:4]=[N:3][C:2]([O:19][C:20]4[CH:29]=[CH:28][CH:27]=[C:26]5[C:21]=4[CH:22]=[CH:23][N:24]=[CH:25]5)=[C:7]([C:8]4[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=4)[CH:6]=3)[CH:29]=[CH:28][CH:27]=2)[CH:22]=[CH:23][N:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 30386Isoquinolin-5-olHCID 21865297HCID 21865297, compound

Product 1

HCID 10459001HCID 10459001, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 3,6-dichloro-4-(4-trifluoromethyl-phenyl)-pyridazine, (Example 45(d)), (100 mg, 0.3 mmol) and 5-hydroxyisoquinoline (112 mg, 0.7 mmol, Aldrich) in DMF (2.5 mL) was added NaH (32 mg, 0.8 mmol, 60 % suspension in mineral oil, Aldrich) and the reaction mixture was heated at 140° C. for 10 min in a microwave synthesizer. The reaction mixture was allowed to cool to room temperature and partitioned between H2O/CH2Cl2. The aqueous layer was extracted with CH2Cl2 and the combined organic layers were concentrated in vacuum. The residue was evaporated onto SiO2 and purified by flash silica gel chromatography with 2M NH3 in MeOH/CH2Cl2 (0:1→1:49) as eluant to give the title compound as an white amorphous solid. Mp: 197-199° C. MS (ESI, pos ion.) m/z: 511 (M+1).

Workup

  1. temperatureto cool to room temperature
  2. custompartitioned between H2O/CH2Cl2
  3. extractionThe aqueous layer was extracted with CH2Cl2
  4. concentrationthe combined organic layers were concentrated in vacuum
  5. customThe residue was evaporated onto SiO2
  6. custompurified by flash silica gel chromatography with 2M NH3 in MeOH/CH2Cl2 (0:1→1:49) as eluant

Sources & evidence

ORD record
ord-e10add4dea724cf497cb5a8ea681e1d5
Source dataset
uspto-grants-2008_02
Patent number
US07332511B2

Reaction notes

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