Ammonium Chloride → HCID 15952174, compound

HRID 1968742Notes

Reaction equation

HRID 1968742 reaction equation
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]

Participants

8

Reactant 4

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

Product 2

HCID 15952174HCID 15952174, compoundYield 27%HCID 136389672HCID 136389672, compoundYield 12%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

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)+.

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-be98dadf8c624b42bd47b207655d0772
Source dataset
uspto-grants-2013_04
Patent number
US08426440B2

Reaction notes

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