Cesium carbonate → HCID 66788462, compound

HRID 576120Notes

Reaction equation

HRID 576120 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)=[CH:16][CH:17]=3)[CH2:12][N:11]([S:28]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[N+:37]([O-:39])=[O:38])(=[O:30])=[O:29])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].Br[C:41]1[N:42]=[CH:43][C:44]([NH2:47])=[N:45][CH:46]=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:41]4[N:42]=[CH:43][C:44]([NH2:47])=[N:45][CH:46]=4)=[CH:16][CH:17]=3)[CH2:12][N:11]([S:28]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=3[N+:37]([O-:39])=[O:38])(=[O:29])=[O:30])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 5995392-Amino-5-bromopyrazineHCID 66789095HCID 66789095, compound

Product 1

HCID 66788462HCID 66788462, compoundYield 14.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-(3,4-dichlorophenyl)-2-(2-nitrophenylsulfonyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroisoquinoline (300 mg, 0.51 mmol), 5-bromopyrazin-2-amine (174 mg, 1.0 mmol) and cesium carbonate (490 mg, 1.5 mmol) in water (1.5 mL) and N,N-dimethylformamide (5 mL) was degassed with argon and then [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (24 mg, 0.03 mmol) was added. The mixture was degassed again and then heated to 90° C. for 3 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 (9:1 hexanes/ethyl acetate to ethyl acetate) to give 5-(4-(3,4-dichlorophenyl)-2-(2-nitrophenylsulfonyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)pyrazin-2-amine (40 mg, 14%) as a yellow oil: ESI MS m/z 556 [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 (9:1 hexanes/ethyl acetate to ethyl acetate)

Sources & evidence

ORD record
ord-f4b2ba9e203b4499b27b9b416881b10e
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

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