Thionyl Chloride → HCID 59743132, compound

HRID 1667514Notes

Reaction equation

HRID 1667514 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]([OH:14])=O)=[CH:9][CH:10]=2)[C:5](=[O:15])[NH:4][N:3]=1.ClC1C2C(=CC=C(C(O)=O)C=2)C(=O)NN=1.S(Cl)(Cl)=O.[F:35][C:36]([F:46])([F:45])[C:37]1[CH:38]=[C:39]([CH:42]=[CH:43][CH:44]=1)[CH2:40][NH2:41].[H-].[Na+]>O.CN(C=O)C>[F:35][C:36]([F:45])([F:46])[C:37]1[CH:38]=[C:39]([CH:42]=[CH:43][CH:44]=1)[CH2:40][NH:41][C:12]([C:8]1[CH:7]=[C:6]2[C:11](=[CH:10][CH:9]=1)[C:2]([Cl:1])=[N:3][NH:4][C:5]2=[O:15])=[O:14]

Participants

8

Reactant 5

HCID 24386Thionyl ChlorideHCID 24758Sodium hydrideHCID 759623-(Trifluoromethyl)benzylamineHCID 67417448HCID 67417448, compoundHCID 67417752HCID 67417752, compound

Product 1

HCID 59743132HCID 59743132, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 1-chloro-4-oxo-3,4-dihydro-phthalazine-6-carboxylic acid and 4-chloro-1-oxo-1,2-dihydro-phthalazine-6-carboxylic acid (311 mg, 1.385 mmol), catalytic DMF and thionyl chloride (7 mL) was refluxed for 3 hours. The solution was cooled, concentrated under vacuum and treated 3 times with toluene in order to remove the excess thionyl chloride. The crude residue was dissolved in DMF (3 mL) and added dropwise to a 0° C. solution of 3-(trifluoromethyl)benzylamine (0.22 mL, 1.524 mmol), DMF (5 mL) and 60% NaH (199 mg, 8.31 mmol). The reaction was stirred at room temperature overnight, diluted with water and extracted with EtOAc (×3). The combined organic layers were washed with water, brine and dried (Na2SO4). Column chromatography (Hex/EtOAc) afforded 1-chloro-4-oxo-3,4-dihydro-phthalazine-6-carboxylic acid 3-trifluoromethyl-benzylamide (30 mg) as a white solid. 1H NMR (400 MHz, d6-DMSO) δ: 4.62 (d, 2H), 7.65 (m, 4H), 8.10 (d, 1H), 8.47 (dd, 1H), 8.80 (d, 1H), 9.65 (t, 1H), 12.99 (s, 1H) ppm; m/z (M+1) 382.17; and 4-chloro-1-oxo-1,2-dihydro-phthalazine-6-carboxylic acid 3-trifluoromethyl-benzylamide (33 mg) as a white solid.

Workup

  1. temperaturewas refluxed for 3 hours
  2. temperatureThe solution was cooled
  3. concentrationconcentrated under vacuum
  4. additiontreated 3 times with toluene in order
  5. customto remove the excess thionyl chloride
  6. dissolutionThe crude residue was dissolved in DMF (3 mL)
  7. extractionextracted with EtOAc (×3)
  8. washThe combined organic layers were washed with water, brine
  9. dry with materialdried (Na2SO4)

Sources & evidence

ORD record
ord-6813b8fc172a49eaa2155e1d7ade3023
Source dataset
uspto-grants-2011_10
Patent number
US08044041B2

Reaction notes

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