Cesium carbonate → HCID 68660870, compound

HRID 576123Notes

Reaction equation

HRID 576123 reaction equation
FC(F)(F)S(O[C:7]1[CH:16]=[C:15]2[C:10]([CH:11]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[CH2:12][N:13]([CH3:17])[CH2:14]2)=[CH:9][C:8]=1[F:25])(=O)=O.BrCC(C1C=CC(Cl)=CC=1)=O.[C:39]([C:42]1[CH:47]=[CH:46][C:45](B(O)O)=[CH:44][CH:43]=1)(=[O:41])[NH2:40].C(=O)([O-])[O-].[Cs+].[Cs+]>O.CN(C)C=O>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([CH:11]2[C:10]3[C:15](=[CH:16][C:7]([C:45]4[CH:46]=[CH:47][C:42]([C:39]([NH2:40])=[O:41])=[CH:43][CH:44]=4)=[C:8]([F:25])[CH:9]=3)[CH2:14][N:13]([CH3:17])[CH2:12]2)=[CH:19][CH:20]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 68303p-Chlorophenacyl bromideHCID 27378114-Aminocarbonylphenylboronic acidHCID 86647721HCID 86647721, compound

Product 1

HCID 68660870HCID 68660870, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-(4-chlorophenyl)-6-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl trifluoromethanesulfonate (695 mg, 1.64 mmol) which was prepared using similar methods described in Step A to Step E of Example 26 starting from 2-bromo-1-(4-chlorophenyl)ethanone, 4-carbamoylphenylboronic acid (406 mg, 2.46 mmol) and cesium carbonate (1.6 mg, 4.92 mmol) in water (5 mL) and N,N-dimethylformamide (20 mL) was degassed with argon and then [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) (59 mg, 0.08 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 preparative HPLC followed by preparative thin-layer chromatography (90:10:1 diethyl ether/methanol/concentrated ammonium hydroxide) to give 4-(4-(4-chlorophenyl)-6-fluoro-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)benzamide (204 mg, 32%) as an off-white solid: ESI MS m/z 395 [M+H]+.

Workup

  1. customwas prepared
  2. customwas degassed with argon
  3. customThe mixture was degassed again
  4. customThe mixture was partitioned between water and ethyl acetate (3×)
  5. washthe combined organic extracts were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-3423d5d58c3b449d86eaac350183db07
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

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