Ammonia → 4-Methyl-3-(1-morpholinophthalazin-6-yl)benzamide

HRID 2357595Notes

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.N.O1CCOCC1.C([N:37](C(C)C)CC)(C)C>S(Cl)(Cl)=O.CCOC(C)=O>[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:37])=[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

Participants

Conditions

Temperature: 70 °C

Procedure

4-Methyl-3-(1-morpholinophthalazin-6-yl)benzoic acid (86 mg, 0.25 mmol) was dissolved in thionyl chloride (3.6 mL) and heated to 70° C. for 2 h. The reaction mixture was concentrated in vacuo before ammonia, 0.5 M in 1,4-dioxane (10 mL, 4.9 mmol) and diisopropylethylamine (0.2 mL, 1.2 mmol) were added. The reaction mixture was heated to 50° C. for 5 h and stirred overnight at RT. The reaction was diluted with 100 mL of EtOAc, added to an addition funnel and partitioned with sodium bicarbonate (saturated, aqueous). The organic layers were washed 3 times 75 mL of sodium bicarbonate (saturated, aqueous), combined, dried over sodium sulfate, and concentrated via rotovap to give a crude product. The crude was purified by chromatography to obtain the title compound. Found MS (ES+): 349(M+H)+.

Workup

temperatureThe reaction mixture was heated to 50° C. for 5 h
additionadded to an addition funnel
custompartitioned with sodium bicarbonate (saturated, aqueous)
washThe organic layers were washed 3 times 75 mL of sodium bicarbonate (saturated, aqueous)
dry with materialdried over sodium sulfate
concentrationconcentrated via rotovap
customto give a crude product
customThe crude was purified by chromatography

Sources & evidence

ORD record: ord-c516d2b566654806b618e5d3770ff22d
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07759337B2

Reaction notes

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