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

HRID 505220ノート

反応式

HRID 505220 の反応式
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

参加物

7

反応物 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

生成物 1

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

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, 0.60 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)+.

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-a04a0a2e47644ae89719943bf93ffe1b
出典データセット
uspto-grants-2010_08
特許番号
US07781438B2

反応ノート

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