Imidazole → HCID 21098845, compound

HRID 1351950Notes

Reaction equation

HRID 1351950 reaction equation
C[C@@:2]1([C:5]2[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=2)[CH2:4][O:3]1.[NH2:11][C@H:12]([CH3:27])[CH2:13][C:14]1[C:22]2[C:17](=[C:18]([C:23]([O:25][CH3:26])=[O:24])[CH:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1.N1C=CN=C1.[CH2:33]([Si:35](Cl)([CH2:38][CH3:39])[CH2:36][CH3:37])[CH3:34]>CO.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[N:7]1[CH:8]=[CH:9][CH:10]=[C:5]([C@@H:2]([O:3][Si:35]([CH2:38][CH3:39])([CH2:36][CH3:37])[CH2:33][CH3:34])[CH2:4][NH:11][C@H:12]([CH3:27])[CH2:13][C:14]2[C:22]3[C:17](=[C:18]([C:23]([O:25][CH3:26])=[O:24])[CH:19]=[CH:20][CH:21]=3)[NH:16][CH:15]=2)[CH:6]=1

Participants

8

Reactant 4

HCID 795ImidazoleHCID 13819ChlorotriethylsilaneHCID 86604024HCID 86604024, compoundHCID 86604025HCID 86604025, compound

Product 1

HCID 21098845HCID 21098845, compoundYield 24.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl (R)-(pyridin-3-yl)oxirane (1.17 g, 9.7 mmol) and methyl (R)-3-(2-aminopropyl)-1H-indole-7-carboxylate (1.50 g, 6.5 mmol) in methanol (10 mL) is stirred at 100° C. for 2 hours under sealed conditions, and the mixture is cooled and concentrated. The residue is dissolved in N,N-dimethylformamide (20 mL), and thereto are added imidazole (1.70 g, 25 mmol) and 4-dimethylaminopyridine (61 mg, 0.5 mmol) and triethylsilyl chloride (3.25 mL, 19.4 mmol). The mixture is stirred at room temperature for 3 hours, and thereto are added ethyl acetate. The mixture is washed with a saturated aqueous sodium hydrogen carbonate solution, water, and a saturated brine, dried over sodium sulfate, and concentrated. The residue is purified by silica gel column chromatography (methanol/chloroform=1/50) to give the desired methyl 3-[(2R)-2-(2-pyridin-3-yl-(2 R)-2-(triethylsilyloxy)ethyl-amino)propyl]-1H-indole-7-carboxylate (0.74 g, yield: 24%).

Workup

  1. temperaturethe mixture is cooled
  2. concentrationconcentrated
  3. dissolutionThe residue is dissolved in N,N-dimethylformamide (20 mL)
  4. washThe mixture is washed with a saturated aqueous sodium hydrogen carbonate solution, water
  5. dry with materiala saturated brine, dried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue is purified by silica gel column chromatography (methanol/chloroform=1/50)

Sources & evidence

ORD record
ord-d240c1cd55ab48808557f8daf31629be
Source dataset
uspto-grants-2007_05
Patent number
US07217724B2

Reaction notes

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