Chloroform → ITK inhibitor 2

HRID 2068888ノート

反応式

HRID 2068888 の反応式
[CH3:1][C:2]1([CH3:22])[CH2:10][C:9]2[NH:8][N:7]=[C:6]([C:11]3[NH:12][C:13]4[C:18]([CH:19]=3)=[CH:17][CH:16]=[C:15]([NH:20][CH3:21])[CH:14]=4)[C:5]=2[CH2:4][CH2:3]1.[N:23]1([C@@H:29]([CH3:33])[C:30]([OH:32])=O)[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1.Cl.C(N=C=NCCCN(C)C)C.C(Cl)(Cl)Cl>N1C=CC=CC=1.O>[CH3:1][C:2]1([CH3:22])[CH2:10][C:9]2[NH:8][N:7]=[C:6]([C:11]3[NH:12][C:13]4[C:18]([CH:19]=3)=[CH:17][CH:16]=[C:15]([N:20]([CH3:21])[C:30](=[O:32])[C@@H:29]([N:23]3[CH2:24][CH2:25][O:26][CH2:27][CH2:28]3)[CH3:33])[CH:14]=4)[C:5]=2[CH2:4][CH2:3]1

参加物

7

反応物 4

HCID 6212ChloroformHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 7059243(S)-2-Morpholin-4-yl-propionic acidHCID 136127299N-[2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl]-N-methylamine

生成物 1

HCID 135980528ITK inhibitor 2収率 78%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 1049Pyridine溶媒

実験手順

To a solution of N-{2-(6,6-dimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-1H-indol-6-yl}-N-methylamine (45 mg, 0.15 mmol) in pyridine (1 ml) were added (S)-2-(morpholin-4-yl)propionic acid obtained in Reference Example 3 (110 mg, 0.69 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (106 mg, 0.55 mmol) at room temperature, and the mixture was stirred for 14 hr. To the reaction mixture were added chloroform and water, and the organic layer was separated. The organic layer was dried over sodium sulfate. Sodium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. Then, the residue was dissolved in a mixed solvent of tetrahydrofuran (1 ml) and methanol (1 ml). To the solution was added 2 N aqueous sodium hydroxide solution (0.35 ml) at room temperature, and the mixture was stirred for 20 min. To the reaction mixture were added chloroform and water, and the organic layer was separated. The organic layer was dried over sodium sulfate. Sodium sulfate was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by thin layer silica gel chromatography to give the title compound (52 mg, yield 78%).

後処理

  1. customthe organic layer was separated
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. customSodium sulfate was removed by filtration
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. dissolutionThen, the residue was dissolved in a mixed solvent of tetrahydrofuran (1 ml) and methanol (1 ml)
  6. additionTo the solution was added 2 N aqueous sodium hydroxide solution (0.35 ml) at room temperature
  7. stirringthe mixture was stirred for 20 min
  8. additionTo the reaction mixture were added chloroform and water
  9. customthe organic layer was separated
  10. dry with materialThe organic layer was dried over sodium sulfate
  11. customSodium sulfate was removed by filtration
  12. concentrationthe filtrate was concentrated under reduced pressure
  13. customThe residue was purified by thin layer silica gel chromatography

出典と根拠

ORDレコード
ord-7e1d6b55dd0e4e3280f2728c69be2888
出典データセット
uspto-grants-2012_10
特許番号
US08299070B2

反応ノート

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