Ammonium Chloride → 3-(7-Chloro-2-dimethylaminomethyl-quinolin-8-yl)-4-(7-methyl-1H-indol-3-yl)-pyrrole-2,5-dione

HRID 1968733노트

반응식

HRID 1968733 반응식
CC(C)([O-])C.[K+].CO[C:9](=[O:22])[C:10]([C:12]1[C:20]2[C:15](=[C:16]([CH3:21])[CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)=O.[Cl:23][C:24]1[C:33]([CH2:34][C:35]([NH2:37])=[O:36])=[C:32]2[C:27]([CH:28]=[CH:29][C:30]([CH2:38][N:39]([CH3:41])[CH3:40])=[N:31]2)=[CH:26][CH:25]=1.[NH4+].[Cl-]>O1CCCC1.CCOC(C)=O>[Cl:23][C:24]1[C:33]([C:34]2[C:35](=[O:36])[NH:37][C:9](=[O:22])[C:10]=2[C:12]2[C:20]3[C:15](=[C:16]([CH3:21])[CH:17]=[CH:18][CH:19]=3)[NH:14][CH:13]=2)=[C:32]2[C:27]([CH:28]=[CH:29][C:30]([CH2:38][N:39]([CH3:40])[CH3:41])=[N:31]2)=[CH:26][CH:25]=1

참가 물질

7

반응물 4

HCID 25517Ammonium ChlorideHCID 11241405Methyl 7-methyl-alpha-oxo-1H-indole-3-acetateHCID 23665647Potassium tert-butoxideHCID 668814632-(7-Chloro-2-dimethylaminomethyl-quinolin-8-yl)-acetamide

생성물 1

HCID 159521733-(7-Chloro-2-dimethylaminomethyl-quinolin-8-yl)-4-(7-methyl-1H-indol-3-yl)-pyrrole-2,5-dione수율 71.9%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

Potassium tert-butoxide (1.0 M in THF, 0.60 ml, 0.60 mmol, 3.0 equiv) was added at room temperature under an atmosphere of argon to a solution of (7-methyl-1H-indol-3-yl)-oxo-acetic acid methyl ester (65 mg, 0.30 mmol, 1.5 equiv) and of 2-(7-chloro-2-dimethylaminomethyl-quinolin-8-yl)-acetamide (55 mg, 0.20 mmol) in anhydrous tetrahydrofuran (2.0 ml, dried over molecular sieves). The reaction mixture was stirred for 15 minutes at room temperature. It was then diluted with EtOAc and poured into a saturated aqueous NH4Cl solution. After three extractions with EtOAc, the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. Purification of the residue via preparative HPLC afforded the title compound (64 mg, 58%) as its trifluoroacetate salt. 1H NMR (400 MHz, d6-DMSO): δ=11.90 (br s, 1H), 11.18 (s, 1H), 9.72 (br s, 1H), 8.59 (d, J=8.2 Hz, 1H), 8.19 (d, J=9.2 Hz, 1H), 7.98 (d, J=2.6 Hz, 1H), 7.77 (d, J=8.8 Hz, 1H), 7.61 (d, J=8.8 Hz, 1H), 6.73 (d, J=7.3 Hz, 1H), 6.33 (t, J=7.3 Hz, 1H), 5.94 (d, J=7.3 Hz, 1H), 4.59 (s, 2H), 2.69 (br s, 6H), 2.38 (s, 3H). MS (ES+): 445.3 (M+H)+.

후처리

  1. extractionAfter three extractions with EtOAc
  2. dry with materialthe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue via preparative HPLC

출처 및 근거

ORD 기록
ord-6ba44c87fbee4d89b5e7bf4e706dee47
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08426440B2

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