Methanol → N-Cyclopropyl-3-fluoro-5-(4-formyl-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide

HRID 906402Notes

Reaction equation

HRID 906402 reaction equation
C([O:4][CH2:5][C:6]([CH3:23])([CH3:22])[CH2:7][N:8]1[CH:17]=[C:16]([CH:18]=[O:19])[C:15]2[C:10](=[CH:11][CH:12]=[C:13](Br)[CH:14]=2)[C:9]1=[O:21])(=O)C.[CH:24]1([NH:27][C:28](=[O:46])[C:29]2[CH:34]=[C:33](B3OC(C)(C)C(C)(C)O3)[C:32]([CH3:44])=[C:31]([F:45])[CH:30]=2)[CH2:26][CH2:25]1.C(=O)([O-])[O-].[K+].[K+].CO>CN(C=O)C.O>[CH:24]1([NH:27][C:28](=[O:46])[C:29]2[CH:34]=[C:33]([C:13]3[CH:14]=[C:15]4[C:10](=[CH:11][CH:12]=3)[C:9](=[O:21])[N:8]([CH2:7][C:6]([CH3:22])([CH3:23])[CH2:5][OH:4])[CH:17]=[C:16]4[CH:18]=[O:19])[C:32]([CH3:44])=[C:31]([F:45])[CH:30]=2)[CH2:25][CH2:26]1

Participants

7

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 866409623-(6-Bromo-4-formyl-1-oxoisoquinolin-2(1H)-yl)-2,2-dimethylpropyl acetate

Product 1

HCID 86640963N-Cyclopropyl-3-fluoro-5-(4-formyl-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamideYield 101.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

A solution of 3-(6-bromo-4-formyl-1-oxoisoquinolin-2(1H)-yl)-2,2-dimethylpropyl acetate (Example 1e, 0.25 g) in DMF (10 mL) was treated with N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.28 g), Pd-118 (0.024 g) and potassium carbonate (0.31 g) under nitrogen. The resulting mixture was stirred at 70° C. for 6 h. Methanol (10 mL) was added and stirred at room temperature for 1 h. The reaction mixture was diluted with water (250 mL), and extracted with ethyl acetate (300 mL). The organic was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified (SiO2 chromatography, elution with 100% ethyl acetate) to afford the subtitle compound (0.30 g) as an oil.

Workup

  1. stirringstirred at room temperature for 1 h
  2. extractionextracted with ethyl acetate (300 mL)
  3. dry with materialThe organic was dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customto afford crude product
  7. customThe crude product was purified
  8. wash(SiO2 chromatography, elution with 100% ethyl acetate)

Sources & evidence

ORD record
ord-7d92c12ce7344c58967dd8ffdf1a24cf
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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