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

HRID 506992ノート

反応式

HRID 506992 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-8f6a3972da0449c5ae9d01fcc0c4d5b6
出典データセット
uspto-grants-2010_08
特許番号
US07786115B2

反応ノート

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