Potassium Carbonate → HCID 59285292, compound

HRID 906432Notes

Reaction equation

HRID 906432 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][C:14]([CH3:25])([CH3:24])[CH2:15][O:16][Si](C(C)(C)C)(C)C)[CH:6]=[C:5]2[CH2:26][N:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][CH2:35][OH:36])[CH2:29][CH2:28]1.[CH:37]1([NH:40][C:41](=[O:59])[C:42]2[CH:47]=[C:46](B3OC(C)(C)C(C)(C)O3)[C:45]([CH3:57])=[C:44]([F:58])[CH:43]=2)[CH2:39][CH2:38]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.[Cl-].[Na+].O>[CH:37]1([NH:40][C:41](=[O:59])[C:42]2[CH:47]=[C:46]([C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[C:8](=[O:12])[N:7]([CH2:13][C:14]([CH3:25])([CH3:24])[CH2:15][OH:16])[CH:6]=[C:5]4[CH2:26][N:27]3[CH2:28][CH2:29][N:30]([CH2:33][CH2:34][CH2:35][OH:36])[CH2:31][CH2:32]3)[C:45]([CH3:57])=[C:44]([F:58])[CH:43]=2)[CH2:38][CH2:39]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 67390786HCID 67390786, compound

Product 1

HCID 59285292HCID 59285292, compoundYield 17.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A solution of 6-bromo-2-(3-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylpropyl)-4-{[4-(3-hydroxypropyl)piperazin-1-yl]methyl}isoquinolin-1(2H)-one (Example 32a, 1.0 g), N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.165 g), potassium carbonate (0.143 g) and Pd-118 (0.034 g) was stirred in DMF (10 mL) at 80° C. under nitrogen for 2 h. The reaction was cooled, diluted with saturated brine and extracted into ethyl acetate (3×30 mL), the combined extracts were washed with brine (3×30 mL), dried, (MgSO4) filtered and evaporated. The residue was dissolved in DCM (20 mL), treated with trifluoroacetic acid (3 mL) and stirred at room temperature for 3 h, evaporated and purified by preparative HPLC (Waters Xbridge column using a 95-5% gradient of aqueous 0.2% ammonia in acetonitrile as eluent) to give the title compound (0.052 g) as a solid.

Workup

  1. temperatureThe reaction was cooled
  2. extractionextracted into ethyl acetate (3×30 mL)
  3. washthe combined extracts were washed with brine (3×30 mL)
  4. customdried
  5. filtration(MgSO4) filtered
  6. customevaporated
  7. dissolutionThe residue was dissolved in DCM (20 mL)
  8. additiontreated with trifluoroacetic acid (3 mL)
  9. customevaporated
  10. custompurified by preparative HPLC (Waters Xbridge column

Sources & evidence

ORD record
ord-cdc175ac1d2f4c0fad6ed932f1612b14
Source dataset
uspto-grants-2011_09
Patent number
US08012980B2

Reaction notes

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