Imidazole → Tert-butyl (3-((tert-butyldimethylsilyl)oxy)-1-(2-(6-chloro-4-(isopropylamino)nicotinoyl)hydrazinyl)-1-oxopropan-2-yl)carbamate

HRID 877579Notes

Reaction equation

HRID 877579 reaction equation
[Cl:1][C:2]1[CH:24]=[C:23]([NH:25][CH:26]([CH3:28])[CH3:27])[C:5]([C:6]([NH:8][NH:9][C:10](=[O:22])[CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:12][OH:13])=[O:7])=[CH:4][N:3]=1.N1C=CN=C1.[C:34]([Si:38](Cl)([CH3:40])[CH3:39])([CH3:37])([CH3:36])[CH3:35]>C(Cl)Cl>[Si:38]([O:13][CH2:12][CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:18])[CH3:19])[C:10]([NH:9][NH:8][C:6](=[O:7])[C:5]1[C:23]([NH:25][CH:26]([CH3:28])[CH3:27])=[CH:24][C:2]([Cl:1])=[N:3][CH:4]=1)=[O:22])([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:40])[CH3:39]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 131732603Tert-butyl (1-(2-(6-chloro-4-(isopropylamino)nicotinoyl)hydrazinyl)-3-hydroxy-1-oxopropan-2-yl)carbamate

Product 1

HCID 131732604Tert-butyl (3-((tert-butyldimethylsilyl)oxy)-1-(2-(6-chloro-4-(isopropylamino)nicotinoyl)hydrazinyl)-1-oxopropan-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

tert-butyl (1-(2-(6-chloro-4-(isopropylamino)nicotinoyl)hydrazinyl)-3-hydroxy-1-oxopropan-2-yl)carbamate (53) (1 g, 2 mmol) in DCM (10 mL), imidazole (7 mmol, 3 equiv.) was added and stirred at room temperature for 10 min. Reaction mixture was cooled to 0° C., t-butyl dimethyl silyl chloride (3.6 mmol, 1.5 equiv.) was added in portions and stirred the reaction mixture overnight at room temperature. Diluted the reaction mixture using DCM, the DCM layer was washed with water. The organic layer was collected, dried over Na2SO4, filtered and concentrated to get tert-butyl (3-((tert-butyldimethylsilyl)oxy)-1-(2-(6-chloro-4-(isopropylamino)nicotinoyl)hydrazinyl)-1-oxopropan-2-yl)carbamate (54). LC/MS: Purospher@star RP-18, 4×55 mm, 3 μm; Solvent A=10% ACN: 90% H2O: 20 mM NH4OAc; Solvent B=90% ACN: 10% H2O: 20 mM NH4COOAc; gradient 0-100% B over 1.5 min (3.2 min run time); retention time: 2.319 min; LCMS (ES-API), m/z 530.2 (M+H).

Workup

  1. customReaction mixture
  2. temperaturewas cooled to 0° C.
  3. stirringstirred the reaction mixture overnight at room temperature
  4. additionDiluted the reaction mixture
  5. washthe DCM layer was washed with water
  6. customThe organic layer was collected
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-70b2a3e86bc84878a06ff36ed168457f
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

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