Dimethylformamide → 3-[7-[3-(dimethylamino)propyl]-1-oxoisoquinolin-2(1H)-yl]-N-isoxazol-3-yl-4-methylbenzamide

HRID 506992Notes

Reaction equation

HRID 506992 reaction equation
[CH3:1][N:2]([CH3:27])[CH2:3][CH2:4][CH2:5][C:6]1[CH:15]=[C:14]2[C:9]([CH:10]=[CH:11][N:12]([C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=3[CH3:26])[C:20]([OH:22])=O)[C:13]2=[O:16])=[CH:8][CH:7]=1.C(Cl)(=O)C(Cl)=O.CN(C=O)C.[NH2:39][C:40]1[CH:44]=[CH:43][O:42][N:41]=1>C(Cl)Cl.CO>[CH3:27][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][C:6]1[CH:15]=[C:14]2[C:9]([CH:10]=[CH:11][N:12]([C:17]3[CH:18]=[C:19]([CH:23]=[CH:24][C:25]=3[CH3:26])[C:20]([NH:39][C:40]3[CH:44]=[CH:43][O:42][N:41]=3)=[O:22])[C:13]2=[O:16])=[CH:8][CH:7]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 18102163-IsoxazolamineHCID 670185853-[7-[3-(dimethylamino)propyl]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoic acid

Product 1

HCID 116261413-[7-[3-(dimethylamino)propyl]-1-oxoisoquinolin-2(1H)-yl]-N-isoxazol-3-yl-4-methylbenzamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 3-[7-[3-(dimethylamino)propyl]-1-oxoisoquinolin-2(1H)-yl]-4-methylbenzoic acid (151 mg) in methylene chloride (3 ml) was cooled to 0° C. and oxalyl chloride (72 μl) was added. After the addition of DMF (25 μl), the reaction mixture was stirred at room temperature for 2 hours, 3-aminoisoxazole (153 μl) was added and stirring continued at room temperature for 2.5 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 yielded an orange oil. The oil was triturated with water resulted in a solid which was collected by filtration washed with diethyl ether and air dried to give 3-[7-[3-(dimethylamino)propyl]-1-oxoisoquinolin-2(1H)-yl]-N-isoxazol-3-yl-4-methylbenzamide as a tan solid (124 mg); NMR Spectrum: (DMSOd6) 0.57 (m, 2H), 0.71 (m, 2H), 1.35 (s, 3H), 2.09 (s, 3H), 6.64 (d, 1H), 7.10 (d, 1H), 7.23 (m, 1H), 7.45 (d, 1H), 7.59 (m, 3H), 7.72 (s, 1H), 7.83 (d, 1H), 8.63 (s, 1H), 9.98 (s, 1H); Mass Spectrum: M+H+ 349.

Workup

  1. stirringstirring
  2. waitcontinued at room temperature for 2.5 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. customyielded an orange oil
  6. customThe oil was triturated with water
  7. customresulted in a solid which
  8. filtrationwas collected by filtration
  9. washwashed with diethyl ether and air
  10. customdried

Sources & evidence

ORD record
ord-8f6a3972da0449c5ae9d01fcc0c4d5b6
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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