Imidazole → HCID 86708700, compound

HRID 921799Notes

Reaction equation

HRID 921799 reaction equation
FC(F)(F)S([O:6][Si:7]([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8])(=O)=O.[Cl:16][C:17]1[C:22]([C:23]([N:25]2[CH2:29][CH:28]([N:30]3[CH2:35][CH2:34][N:33]([CH3:36])[CH2:32][CH2:31]3)[CH:27](O)[CH2:26]2)=[O:24])=[CH:21][C:20]([C:38]#[N:39])=[CH:19][C:18]=1[NH:40][C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44].N1C=CN=C1>CN(C=O)C.C(OCC)(=O)C>[Si:7]([O:6][CH:27]1[CH:28]([N:30]2[CH2:31][CH2:32][N:33]([CH3:36])[CH2:34][CH2:35]2)[CH2:29][N:25]([C:23]([C:22]2[C:17]([Cl:16])=[C:18]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:44])([CH3:45])[CH3:46])[CH:19]=[C:20]([C:38]#[N:39])[CH:21]=2)=[O:24])[CH2:26]1)([C:10]([CH3:13])([CH3:12])[CH3:11])([CH3:9])[CH3:8]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 86708698HCID 86708698, compound

Product 1

HCID 86708700HCID 86708700, compoundYield 81.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

tert-Butyldimethylsilyl trifluoromethanesulfonate (0.240 mL, 1.026 mmol) was added to a solution of (+/−)-tert-butyl (2-chloro-5-cyano-3-(3-hydroxy-4-(4-methylpiperazin-1-yl)pyrrolidine-1-carbonyl)phenyl)carbamate (119 mg, 0.256 mmol) and imidazole (69.8 mg, 1.026 mmol) in DMF (3 mL) and the reaction solution was stirred at room temperature over the weekend. The reaction mixture was diluted with ethyl acetate and washed with saturated sodium bicarbonate. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo, the crude product was purified by flash chromatography on silica gel using an automated ISCO system (40 g column, eluting with 1-6% methanol/dichloromethane). (+/−)-tert-butyl (3-(3-((tert-butyldimethylsilyl)oxy)-4-(4-methylpiperazin-1-yl)pyrrol idine-1-carbonyl)-2-chloro-5-cyanophenyl)carbamate (120 mg) was obtained as a colorless oil.

Workup

  1. washwashed with saturated sodium bicarbonate
  2. dry with materialThe organic layer was dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customthe crude product was purified by flash chromatography on silica gel using
  6. washan automated ISCO system (40 g column, eluting with 1-6% methanol/dichloromethane)

Sources & evidence

ORD record
ord-b7f07217b72c44c38c92b776cf3e623c
Source dataset
uspto-grants-2016_03
Patent number
US09273057B2

Reaction notes

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