Dimethylformamide → HCID 11619795, compound

HRID 506996Notes

Reaction equation

HRID 506996 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[N:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][C:15]([CH2:21][CH2:22][CH2:23][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[CH:16][CH:17]=2)[C:12]1=[O:30].C(Cl)(=O)C(Cl)=O.CN(C=O)C.[NH2:42][C:43]1[CH:47]=[CH:46][O:45][N:44]=1>C(Cl)Cl.CO.C(OCC)(=O)C>[O:45]1[CH:46]=[CH:47][C:43]([NH:42][C:6](=[O:8])[C:5]2[CH:9]=[CH:10][C:2]([CH3:1])=[C:3]([N:11]3[CH:20]=[CH:19][C:18]4[C:13](=[CH:14][C:15]([CH2:21][CH2:22][CH2:23][N:24]5[CH2:25][CH2:26][O:27][CH2:28][CH2:29]5)=[CH:16][CH:17]=4)[C:12]3=[O:30])[CH:4]=2)=[N:44]1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 18102163-IsoxazolamineHCID 67018568HCID 67018568, compound

Product 1

HCID 11619795HCID 11619795, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 4-methyl-3-[7-(3-morpholin-4-ylpropyl)-1-oxoisoquinolin-2(1H)-yl]benzoic acid (140 mg) in methylene chloride (3 ml) was cooled to 0° C. and oxalyl chloride (59 μl) was added. After the addition of DMF (25 μl), the reaction mixture was stirred at room temperature for 2 hours, 3-aminoisoxazole (126 μl) was added and stirring continued at room temperature for 3.5 hours. The reaction mixture was dissolved in methanol and water and purified by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK) using initially methanol and then a 99:1 mixture of methanol and aqueous ammonia solution to give a brown oil. The oil was dissolved in ethyl acetate and the insoluble material was removed by filteration. The filtrate was washed with water, brine, dried (magnesium sulfate) and concentrated to a brown oil. Purification by column chromatography on a silica column eluting using a gradient of ethyl acetate to 10% methanol/ethyl acetate gave N-isoxazol-3-yl-4-methyl-3-[7-(3-morpholin-4-ylpropyl)-1-oxoisoquinolin-2(1H)-yl]benzamide as a yellow foam (55 mg); NMR Spectrum: (DMSOd6) 1.80 (m, 2H), 2.15 (s, 3H), 2.28-2.36 (m, 6H), 2.78 (t, 2H), 3.58 (t, 4H), 6.75 (d, 1H), 7.05 (s, 1H), 7.33 (d, 1H), 7.59 (d, 1H), 7.68 (m, 2H), 8.01 (s, 1H), 8.06 (d, 1H), 8.10 (s, 1H), 8.85 (s, 1H), 11.47 (s, 1H); Mass Spectrum: M+H+ 473.

Workup

  1. stirringstirring
  2. waitcontinued at room temperature for 3.5 hours
  3. customwater and purified by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK)
  4. additiona 99:1 mixture of methanol and aqueous ammonia solution
  5. customto give a brown oil
  6. customthe insoluble material was removed by filteration
  7. washThe filtrate was washed with water, brine
  8. dry with materialdried (magnesium sulfate)
  9. concentrationconcentrated to a brown oil
  10. customPurification by column chromatography on a silica column
  11. washeluting

Sources & evidence

ORD record
ord-576114d1c8674f849e568c49f919f294
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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