Ammonium Chloride → 3-[6-[tert-butylsilyloxy(diphenyl)methyl]-2-methylimidazo[1,2-a]pyridin-3-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dione

HRID 216675

Reaction equation

HRID 216675 reaction equation
CC(C)([O-])C.[K+].CO[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.[C:22]([SiH2:26][O:27][C:28]([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:29]1[CH:30]=[CH:31][C:32]2[N:33]([C:35]([CH2:39][C:40]([NH2:42])=[O:41])=[C:36]([CH3:38])[N:37]=2)[CH:34]=1)([CH3:25])([CH3:24])[CH3:23].[NH4+].[Cl-]>O1CCCC1.CCOC(C)=O>[C:22]([SiH2:26][O:27][C:28]([C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1)([C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)[C:29]1[CH:30]=[CH:31][C:32]2[N:33]([C:35]([C:39]3[C:40](=[O:41])[NH:42][C:9](=[O:21])[C:10]=3[C:12]3[C:20]4[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=4)[NH:14][CH:13]=3)=[C:36]([CH3:38])[N:37]=2)[CH:34]=1)([CH3:25])([CH3:23])[CH3:24]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 588944Methyl 3-indoleglyoxylateHCID 23665647Potassium tert-butoxideHCID 1317297552-[6-(Tert-butyl-diphenyl-silanyloxymethyl)-2-methyl-imidazo[1,2-a]pyridin-3-yl]-acetamide

Product 1

HCID 1317297543-[6-[tert-butylsilyloxy(diphenyl)methyl]-2-methylimidazo[1,2-a]pyridin-3-yl]-4-(1H-indol-3-yl)pyrrole-2,5-dioneYield 47.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
45 °C

Procedure

Potassium tert-butoxide (1.0 M in THF, 1.90 ml, 1.90 mmol, 3.0 equiv) is added dropwise at room temperature under an atmosphere of argon to a solution of (1H-Indol-3-yl)-oxo-acetic acid methyl ester (192 mg, 0.93 mmol, 1.5 equiv) and of 2-[6-(tert-butyl-diphenyl-silanyloxymethyl)-2-methyl-imidazo[1,2-a]pyridin-3-yl]-acetamide (300 mg, 0.62 mmol) in anhydrous tetrahydrofuran (5.0 ml, dried over molecular sieves). The reaction mixture is stirred for 30 minutes at 0° C., 30 minutes at room temperature and 1 hour at 45° C. It is then diluted with EtOAc and poured into a saturated aqueous NH4Cl solution. After three extractions with EtOAc, the combined organic layers are dried over Na2SO4, filtered and concentrated in vacuo. Purification of the residue via flash chromatography (gradient of hexane/EtOAc 50:50 to 20:80) affords the title compound (180 mg, 45%). MS (ES+): 611 (M+H)+.

Workup

  1. extractionAfter three extractions with EtOAc
  2. dry with materialthe combined organic layers are dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification of the residue via flash chromatography (gradient of hexane/EtOAc 50:50 to 20:80)

Sources & evidence

ORD record
ord-2597014dcd6e4282958a78e49cdc96fb
Source dataset
uspto-grants-2012_06
Patent number
US08193236B2

Linked notes

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