Potassium Carbonate → N-Cyclopropyl-3-(2-(cyclopropylmethyl)-4-formyl-1-oxo-1,2-dihydroisoquinolin-6-yl)-5-fluoro-4-methylbenzamide

HRID 907305Notes

Reaction equation

HRID 907305 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][CH:14]1[CH2:16][CH2:15]1)[CH:6]=[C:5]2[CH:17]=[O:18].[CH:19]1([NH:22][C:23](=[O:41])[C:24]2[CH:29]=[C:28](B3OC(C)(C)C(C)(C)O3)[C:27]([CH3:39])=[C:26]([F:40])[CH:25]=2)[CH2:21][CH2:20]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[CH:19]1([NH:22][C:23](=[O:41])[C:24]2[CH:25]=[C:26]([F:40])[C:27]([CH3:39])=[C:28]([C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[C:8](=[O:12])[N:7]([CH2:13][CH:14]3[CH2:16][CH2:15]3)[CH:6]=[C:5]4[CH:17]=[O:18])[CH:29]=2)[CH2:20][CH2:21]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 57551776HCID 57551776, compound

Product 1

HCID 57551841N-Cyclopropyl-3-(2-(cyclopropylmethyl)-4-formyl-1-oxo-1,2-dihydroisoquinolin-6-yl)-5-fluoro-4-methylbenzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of the product of Example 59 step ii) (3.17 g), N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (3.3 g) [prepared as described in WO06110173] and potassium carbonate (2.86 g) in DMF (40 mL) was added Pd-118 (0.20 g) and the mixture heated at 60° C. under nitrogen for 11 hours. The reaction mixture was diluted with ethyl acetate and washed with water and brine. The organics were dried over magnesium sulphate, filtered and evaporated. The residue was purified (SiO2, eluting with 3:2 ethyl acetate:isohexane) to give the sub-title compound (4.24 g).

Workup

  1. washwashed with water and brine
  2. dry with materialThe organics were dried over magnesium sulphate
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified
  6. wash(SiO2, eluting with 3:2 ethyl acetate:isohexane)

Sources & evidence

ORD record
ord-9c6f79d078404770b49513bc9b6b7a9e
Source dataset
uspto-grants-2011_09
Patent number
US08012979B2

Reaction notes

Loading…