Ethylamine → N-ethyl-4-methyl-3-(1-morpholinophthalazin-6-yl)benzamide

HRID 2357637Notes

Reaction equation

HRID 2357637 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[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.[CH3:27][CH2:28][N:29](C(C)C)C(C)C.C(N)C>S(Cl)(Cl)=O.C1COCC1.C(OCC)(=O)C>[CH2:28]([NH:29][C:6](=[O:8])[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[CH2:22][CH2:23][O:24][CH2:25][CH2:26]2)=[N:16][N:15]=[CH:14]3)[CH:4]=1)[CH3:27]

Participants

7

Reactant 3

HCID 6341EthylamineHCID 81531DiisopropylethylamineHCID 251930634-Methyl-3-(1-morpholinophthalazin-6-yl)benzoic acid

Product 1

HCID 68453711N-ethyl-4-methyl-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 before being concentrated in vacuo. The concentrate was dissolved in THF (5.7 mL), and DIPEA (150 μL, 859 μmol) and ethylamine—2 M in THF (0.71 mL) were added at 0° C. The reaction mixture was warmed to RT and stirred for 3 h, then diluted with 50 mL of ethyl acetate, added to a separation funnel, partitioned with sodium bicarbonate (saturated, aqueous), washed 3× with 50 mL of sodium bicarbonate (saturated, aqueous), separated, dried over sodium sulfate, and concentrated in vacuo to give a crude residue, which was purified by chromatography to afford the title compound. MS (ES+): 377(M+H)+.

Workup

  1. concentrationbefore being concentrated in vacuo
  2. dissolutionThe concentrate was dissolved in THF (5.7 mL)
  3. temperatureThe reaction mixture was warmed to RT
  4. additionadded to a separation funnel
  5. custompartitioned with sodium bicarbonate (saturated, aqueous)
  6. washwashed 3× with 50 mL of sodium bicarbonate (saturated, aqueous)
  7. customseparated
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated in vacuo
  10. customto give a crude residue, which
  11. customwas purified by chromatography

Sources & evidence

ORD record
ord-8c56f0757dba4696987fdd5e5f9cce74
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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