Ammonium Chloride → HCID 15952174, 화합물

HRID 1968742노트

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HRID 1968742 반응식
CC(C)([O-:4])C.[K+].C[O:8][C:9](=[O:21])[C:10]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)=O.[Cl:22][C:23]1[C:24]([CH2:37][C:38]([NH2:40])=[O:39])=[C:25]2[C:30](=[CH:31][CH:32]=1)[N:29]=[CH:28][C:27]([CH2:33][N:34]([CH3:36])[CH3:35])=[N:26]2.[NH4+].[Cl-]>O1CCCC1.CCOC(C)=O>[Cl:22][C:23]1[C:24]([C:37]2[C:38](=[O:39])[NH:40][C:9](=[O:21])[C:10]=2[C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[NH:14][CH:13]=2)=[C:25]2[C:30](=[CH:31][CH:32]=1)[N:29]=[CH:28][C:27]([CH2:33][N:34]([CH3:35])[CH3:36])=[N:26]2.[CH3:35][N:34]([CH2:33][C:27]1[CH:28]=[N:29][C:30]2[C:25]([N:26]=1)=[C:24]([C:37]1[C:38](=[O:39])[NH:40][C:9](=[O:8])[C:10]=1[C:12]1[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[NH:14][CH:13]=1)[C:23]([OH:4])=[CH:32][CH:31]=2)[CH3:36]

참가 물질

8

반응물 4

HCID 25517Ammonium ChlorideHCID 588944Methyl 3-indoleglyoxylateHCID 23665647Potassium tert-butoxideHCID 66882585HCID 66882585, 화합물

생성물 2

HCID 15952174HCID 15952174, 화합물수율 27%HCID 136389672HCID 136389672, 화합물수율 12%

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

Potassium tert-butoxide (1.0 M in THF, 0.86 ml, 0.86 mmol, 4.0 equiv) was added at room temperature under an atmosphere of argon to a solution of (1H-indol-3-yl)-oxo-acetic acid methyl ester (66 mg, 0.32 mmol, 1.5 equiv) and of 2-(6-chloro-3-dimethylaminomethyl-quinoxalin-5-yl)-acetamide (60 mg, 0.22 mmol) in anhydrous tetrahydrofuran (3.0 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 (32 mg, 27%) and 3-(3-dimethylaminomethyl-6-hydroxy-quinoxalin-5-yl)-4-(1H-indol-3-yl)-pyrrole-2,5-dione (14 mg, 12%) as their trifluoroacetate salts. Data for 3-(6-chloro-3-dimethylaminomethyl-quinoxalin-5-yl)-4-(1H-indol-3-yl)-pyrrole-2,5-dione: 1H NMR (400 MHz, d6-DMSO): δ=11.97 (s, 1H), 11.26 (s, 1H), 9.86 (s, 1H), 9.01 (s, 1H) 8.29 (d, J=9.0 Hz, 1H), 8.06-8.04 (m, 2H), 7.35 (d, J=8.0 Hz, 1H), 6.96 (dt, J=7.6/1.0 Hz, 1H), 6.49 (dt, J=8.1/1.0 Hz, 1H), 6.09 (d, J=8.3 Hz, 1H), 4.68 (s, 2H), 2.66 (s, 6H). MS (ES+): 432.2 (M+H)+. Data for 3-(3-dimethylaminomethyl-6-hydroxy-quinoxalin-5-yl)-4-(1H-indol-3-yl)-pyrrole-2,5-dione: 1H NMR (400 MHz, d6-DMSO): δ=11.80 (s, 1H), 11.01 (s, 1H), 10.64 (s, 1H), 9.79 (s, 1H), 8.75 (s, 1H), 8.08 (d, J=9.3 Hz, 1H), 7.95 (d, J=2.9 Hz, 1H), 7.51 (d, J=9.0 Hz, 1H), 7.32 (d, J=8.1 Hz, 1H), 6.93 (dt, J=7.6/0.9 Hz, 1H), 6.48 (dt, J=8.1/1.0 Hz, 1H), 6.34 (d, J=8.3 Hz), 4.58 (s, 2H), 2.67 (s, 6H). MS (ES+): 414.3 (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-be98dadf8c624b42bd47b207655d0772
출처 데이터셋
uspto-grants-2013_04
특허 번호
US08426440B2

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