Cesium carbonate → HCID 66788707, compound

HRID 576116Notes

Reaction equation

HRID 576116 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:18]3[C:13](=[CH:14][C:15](B4OC(C)(C)C(C)(C)O4)=[C:16]([F:19])[CH:17]=3)[CH2:12][N:11]([CH3:29])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].Br[C:31]1[CH:39]=[CH:38][C:34]([C:35]([NH2:37])=[O:36])=[CH:33][CH:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O.CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]2[C:18]3[C:13](=[CH:14][C:15]([C:31]4[CH:39]=[CH:38][C:34]([C:35]([NH2:37])=[O:36])=[CH:33][CH:32]=4)=[C:16]([F:19])[CH:17]=3)[CH2:12][N:11]([CH3:29])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 696834-BromobenzamideHCID 66788241HCID 66788241, compound

Product 1

HCID 66788707HCID 66788707, compoundYield 43%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-(3,4-dichlorophenyl)-6-fluoro-2-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline (1.0 g mg, 2.3 mmol), 4-bromobenzamide (690 mg, 3.45 mmol) and cesium carbonate (2.25 g, 6.9 mmol) in water (6 mL) and N,N-dimethylformamide (20 mL) was degassed with argon and then [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (88 mg, 0.12 mmol) was added. The mixture was degassed again and then heated to 90° C. for 2 hours. The mixture was partitioned between water and ethyl acetate (3×) and the combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was partially purified by column chromatography (7:3 hexanes/ethyl acetate to ethyl acetate, then ethyl acetate to 90:9:1 ethyl acetate/methanol/concentrated ammonium hydroxide) to give 4-(4-(3,4-dichlorophenyl)-6-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide (423 mg, 43%) as a brown solid: ESI MS m/z 429 [M+H]+.

Workup

  1. customwas degassed with argon
  2. customThe mixture was degassed again
  3. customThe mixture was partitioned between water and ethyl acetate (3×)
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was partially purified by column chromatography (7:3 hexanes/ethyl acetate to ethyl acetate

Sources & evidence

ORD record
ord-72e465ab09c74e5aaab2770e6308ba94
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

Loading…