Ammonium Chloride → HCID 15952174、化合物

HRID 1968742ノート

反応式

HRID 1968742 の反応式
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]

参加物

8

反応物 4

HCID 25517Ammonium ChlorideHCID 588944Methyl 3-indoleglyoxylateHCID 23665647Potassium tert-butoxideHCID 66882585HCID 66882585、化合物

生成物 2

HCID 15952174HCID 15952174、化合物収率 27%HCID 136389672HCID 136389672、化合物収率 12%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-be98dadf8c624b42bd47b207655d0772
出典データセット
uspto-grants-2013_04
特許番号
US08426440B2

反応ノート

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