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

HRID 505220Notes

Reaction equation

HRID 505220 reaction equation
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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-a04a0a2e47644ae89719943bf93ffe1b
Source dataset
uspto-grants-2010_08
Patent number
US07781438B2

Reaction notes

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