Imidazole → 3-[2-(3-{[tert-Butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-4-formyl-1-oxo-1,2-dihydroisoquinolin-6-yl]-N-cyclopropyl-5-fluoro-4-methylbenzamide

HRID 906423Notes

Reaction equation

HRID 906423 reaction equation
[CH:1]1([NH:4][C:5](=[O:33])[C:6]2[CH:11]=[C:10]([C:12]3[CH:13]=[C:14]4[C:19](=[CH:20][CH:21]=3)[C:18](=[O:22])[N:17]([CH2:23][C:24]([CH3:28])([CH3:27])[CH2:25][OH:26])[CH:16]=[C:15]4[CH:29]=[O:30])[C:9]([CH3:31])=[C:8]([F:32])[CH:7]=2)[CH2:3][CH2:2]1.[C:34]([Si:38]([CH3:41])([CH3:40])Cl)([CH3:37])([CH3:36])[CH3:35].N1C=CN=C1>CN(C=O)C.O>[Si:38]([O:26][CH2:25][C:24]([CH3:27])([CH3:28])[CH2:23][N:17]1[CH:16]=[C:15]([CH:29]=[O:30])[C:14]2[C:19](=[CH:20][CH:21]=[C:12]([C:10]3[CH:11]=[C:6]([CH:7]=[C:8]([F:32])[C:9]=3[CH3:31])[C:5]([NH:4][CH:1]3[CH2:3][CH2:2]3)=[O:33])[CH:13]=2)[C:18]1=[O:22])([C:34]([CH3:37])([CH3:36])[CH3:35])([CH3:41])[CH3:40]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chloride2×HCID 86640963N-Cyclopropyl-3-fluoro-5-(4-formyl-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide

Product 1

HCID 866409693-[2-(3-{[tert-Butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-4-formyl-1-oxo-1,2-dihydroisoquinolin-6-yl]-N-cyclopropyl-5-fluoro-4-methylbenzamideYield 83.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of N-cyclopropyl-3-fluoro-5-[4-formyl-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-6-yl]-4-methylbenzamide (Example 26e, 14.54 g) in DMF (120 mL) was treated with tert-butyldimethylchlorosilane (4.86 g) and imidazole (2.19 g) under nitrogen. The resulting mixture was stirred at room temperature for 1 h. More tert-butyldimethylchlorosilane (1.2 g) was added and the reaction mixture stirred at room temperature for 30 min, diluted with water (300 mL) and extracted with DCM (250 mL×2). The organics were dried (MgSO4), filtered and evaporated. The residue was purified (SiO2 chromatography, elution with 100% diethyl ether) to give the subtitle compound (15.20 g) as a gum.

Workup

  1. stirringthe reaction mixture stirred at room temperature for 30 min
  2. extractionextracted with DCM (250 mL×2)
  3. dry with materialThe organics were dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified
  7. wash(SiO2 chromatography, elution with 100% diethyl ether)

Sources & evidence

ORD record
ord-e88142d3c25d4a44af0c8426ae2c6d1c
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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