Pyridine → N-(isoxazol-3-yl)-4-methyl-3-(1-morpholinophthalazin-6-yl)benzamide

HRID 2357689Notes

Reaction equation

HRID 2357689 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][C:3]=1[C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[C:17]([N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1)=[N:16][N:15]=[CH:14]2.S(Cl)(Cl)=O.[O:31]1[CH:35]=[CH:34][C:33]([NH2:36])=[N:32]1.N1C=CC=CC=1>ClCCl>[O:31]1[CH:35]=[CH:34][C:33]([NH:36][C:6](=[O:7])[C:5]2[CH:9]=[CH:10][C:2]([CH3:1])=[C:3]([C:11]3[CH:12]=[C:13]4[C:18](=[CH:19][CH:20]=3)[C:17]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)=[N:16][N:15]=[CH:14]4)[CH:4]=2)=[N:32]1

Participants

6

Reactant 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 18102163-IsoxazolamineHCID 251930634-Methyl-3-(1-morpholinophthalazin-6-yl)benzoic acid

Product 1

HCID 68453445N-(isoxazol-3-yl)-4-methyl-3-(1-morpholinophthalazin-6-yl)benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-methyl-3-(1-morpholinophthalazin-6-yl)benzoic acid (Example 8, 160 mg, 0.45 mmol) in thionyl chloride (1.0 mL, 1.37 mmol) was stirred at RT for 1 h. Excess SOCl2 was removed under reduced pressure and the residue was treated with 1 mL of toluene and concentrated under reduced pressure. The residue was dissolved in dichloromethane (3 mL), and isoxazol-3-amine (58 mg, 0.69 mmol) followed by pyridine (72 mg, 0.92 mmol) was added. After the resulting mixture was refluxed for 1 h, cooled to RT, diluted with dichloromethane, and washed with 1 N NaOH. The dichloromethane layer was dried, concentrated, and purified on an ISCO 12 g column (eluted with 5-15% MeOH in ethyl acetate) to provide N-(isoxazol-3-yl)-4-methyl-3-(1-morpholinophthalazin-6-yl)benzamide as an amorphous off-white solid. Found MS (ESI, pos. ion) m/z: 416 (M+1).

Workup

  1. customExcess SOCl2 was removed under reduced pressure
  2. additionthe residue was treated with 1 mL of toluene
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in dichloromethane (3 mL)
  5. additionwas added
  6. temperatureAfter the resulting mixture was refluxed for 1 h
  7. washwashed with 1 N NaOH
  8. dry with materialThe dichloromethane layer was dried
  9. concentrationconcentrated
  10. custompurified on an ISCO 12 g column (eluted with 5-15% MeOH in ethyl acetate)

Sources & evidence

ORD record
ord-e5971e4769cc4777af6abb9adfeafc7c
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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