Methylamine → N,4-dimethyl-3-(1-morpholinophthalazin-6-yl)benzamide

HRID 2357593Notes

Reaction equation

HRID 2357593 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.[CH:27]([N:30](C(C)C)CC)(C)C.CN>S(Cl)(Cl)=O.C1COCC1.CCOC(C)=O>[CH3:27][NH:30][C:6](=[O:7])[C:5]1[CH:9]=[CH:10][C:2]([CH3:1])=[C:3]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[C:17]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[N:16][N:15]=[CH:14]3)[CH:4]=1

Participants

7

Reactant 3

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 251930634-Methyl-3-(1-morpholinophthalazin-6-yl)benzoic acid

Product 1

HCID 68452282N,4-dimethyl-3-(1-morpholinophthalazin-6-yl)benzamide

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
65 °C

Procedure

4-Methyl-3-(1-morpholinophthalazin-6-yl)benzoic acid (100 mg, 286 μmol) was dissolved in thionyl chloride (5.7 mL) and heated to 65° C. for 1 h. The reaction was then concentrated in vacuo, dissolved in tetrahydrofuran 99.9% (5.7 mL) and diisopropylethylamine (150 μL, 859 μmol) and methylamine, 2.0 m solution in THF (0.7 mL) were added. The reaction mixture was stirred for 3 h at ambient temperature. The reaction mixture was diluted with 50 mL of EtOAc, added to an addition funnel and partitioned with sodium bicarbonate (saturated, aqueous). The organic layers were washed 3 times with 50 mL of sodium bicarbonate (saturated, aqueous), dried over sodium sulfate, and concentrated via rotovap to give a crude product. After purification by chromatography, the title compound was obtained. Found MS (ES+): 363(M+H)+.

Workup

  1. concentrationThe reaction was then concentrated in vacuo
  2. dissolutiondissolved in tetrahydrofuran 99.9% (5.7 mL)
  3. additionadded to an addition funnel
  4. custompartitioned with sodium bicarbonate (saturated, aqueous)
  5. washThe organic layers were washed 3 times with 50 mL of sodium bicarbonate (saturated, aqueous)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated via rotovap
  8. customto give a crude product
  9. customAfter purification by chromatography

Sources & evidence

ORD record
ord-8953f0acc63446c1a84774c219f57d31
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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