Chloroform → ITK inhibitor 2

HRID 2068888노트

반응식

HRID 2068888 반응식
[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

참가 물질

7

반응물 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

생성물 1

HCID 135980528ITK inhibitor 2수율 78%

시약·촉매·용매 2

HCID 962Water용매HCID 1049Pyridine용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-7e1d6b55dd0e4e3280f2728c69be2888
출처 데이터셋
uspto-grants-2012_10
특허 번호
US08299070B2

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