Cesium carbonate → HCID 66788529, compound

HRID 576114Notes

Reaction equation

HRID 576114 reaction equation
FC(F)(F)S(O[C:7]1[CH:16]=[C:15]2[C:10]([CH:11]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=3)[CH2:12][NH:13][CH2:14]2)=[CH:9][CH:8]=1)(=O)=O.[C:27]([C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1)(=[O:29])[NH2:28].C(=O)([O-])[O-].[Cs+].[Cs+]>O.CN(C)C=O>[Cl:24][C:19]1[CH:18]=[C:17]([CH:11]2[C:10]3[C:15](=[CH:16][C:7]([C:33]4[CH:34]=[CH:35][C:30]([C:27]([NH2:28])=[O:29])=[CH:31][CH:32]=4)=[CH:8][CH:9]=3)[CH2:14][NH:13][CH2:12]2)[CH:22]=[CH:21][C:20]=1[Cl:23]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27378114-Aminocarbonylphenylboronic acidHCID 86647718HCID 86647718, compound

Product 1

HCID 66788529HCID 66788529, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydroisoquinolin-7-yl trifluoromethanesulfonate (225 mg, 0.53 mmol), 4-carbamoylphenylboronic acid (132 mg, 0.8 mmol) and cesium carbonate (521 mg, 1.6 mmol) in water (2 mL) and N,N-dimethylformamide (4 mL) was degassed with argon and then [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (22 mg, 0.03 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 purified by semi-preparative HPLC followed by lyophilization to give 4-(4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide (19 mg, 7%) as a yellow oil: 1H NMR (CD3OD, 500 MHz) δ 7.96 (d, J=8.3 Hz, 2H), 7.74 (d, J=8.3 Hz, 2H), 7.64 (s, 1H), 7.62-7.59 (m, 1H), 7.56 (d, J=8.3 Hz, 1H), 7.49 (d, J=2.0 Hz, 1H), 7.23 (dd, J=8.3, 2.0 Hz, 1H), 7.02 (d, J=8.2 Hz, 1H), 4.67-4.53 (m, 3H), 3.82 (dd, J=12.6, 6.1 Hz, 1H), 3.51 (dd, J=12.5, 10.9 Hz, 1H); ESI MS m/z 397 [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 purified by semi-preparative HPLC

Sources & evidence

ORD record
ord-a8512af011d3401a97ad799db421472d
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

Loading…