1,2-Diaminocyclohexane, trans- → HCID 71145733, compound

HRID 535304Notes

Reaction equation

HRID 535304 reaction equation
[O-]P([O-])([O-])=O.[K+].[K+].[K+].[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C@H:16]2[C:25]3[C:20](=[CH:21][C:22]([O:30][CH3:31])=[C:23]([O:26][CH:27]([CH3:29])[CH3:28])[CH:24]=3)[CH2:19][C:18](=[O:32])[NH:17]2)=[CH:12][CH:11]=1.I[C:34]1[CH:39]=[CH:38][C:37]([C:40]([C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([O:49][CH3:50])[CH:44]=2)([OH:42])[CH3:41])=[CH:36][CH:35]=1.N[C@@H]1CCCC[C@H]1N>C(OCC)(=O)C.[Cu]I.O1CCOCC1>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([C@H:16]2[C:25]3[C:20](=[CH:21][C:22]([O:30][CH3:31])=[C:23]([O:26][CH:27]([CH3:28])[CH3:29])[CH:24]=3)[CH2:19][C:18](=[O:32])[N:17]2[C:34]2[CH:35]=[CH:36][C:37]([C:40]([OH:42])([C:43]3[CH:48]=[CH:47][CH:46]=[C:45]([O:49][CH3:50])[CH:44]=3)[CH3:41])=[CH:38][CH:39]=2)=[CH:14][CH:15]=1

Participants

8

Reactant 4

HCID 438061,2-Diaminocyclohexane, trans-HCID 62657Potassium Phosphate, TribasicHCID 58437804HCID 58437804, compoundHCID 71145829HCID 71145829, compound

Product 1

HCID 71145733HCID 71145733, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A dry 10 ml microwave vial was charged with K3PO4 (123 mg, 0.578 mmol), (S)-1-(4-chlorophenyl)-7-isopropoxy-6-methoxy-1,2-dihydroisoquinolin-3(4H)-one (100 mg, 0.289 mmol), 1-(4-iodophenyl)-1-(3-methoxyphenyl)ethanol (113 mg, 0.318 mmol), trans-1,2-diaminocyclohexane (6.95 μl, 0.058 mmol) and dioxane (3 ml). The reaction mixture was degassed with argon in a sonic bath during 5 minutes. Then copper(I)iodide (11.01 mg, 0.058 mmol) was added. The vial was sealed and heated for 8 hrs to 100° C. in a metal heating block. The reaction mixture was diluted with ethyl acetate and the organic phase was washed with aqueous NaHCO3 solution and brine. The organic phase was dried over Na2SO4, filtered and concentrated in vacuo to obtain a brown oil as crude material which was purified by preparative HPLC (reversed phase). Fractions containing the products were pooled and worked up (addition of NaHCO3, removal of acetonitrile followed by extraction with DCM). The residue was dissolved in 1,4-dioxane and freeze dried overnight to obtain the title compound as yellowish solid.

Workup

  1. customThe reaction mixture was degassed with argon in a sonic bath during 5 minutes
  2. customThe vial was sealed
  3. temperatureheated for 8 hrs to 100° C. in a metal
  4. temperatureheating block
  5. washthe organic phase was washed with aqueous NaHCO3 solution and brine
  6. dry with materialThe organic phase was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto obtain a brown oil as crude material which
  10. customwas purified by preparative HPLC (reversed phase)
  11. additionFractions containing the products
  12. addition(addition of NaHCO3, removal of acetonitrile followed by extraction with DCM)
  13. dissolutionThe residue was dissolved in 1,4-dioxane
  14. customfreeze dried overnight

Sources & evidence

ORD record
ord-f4612bab2c5c45c6a587e8d5159abbdb
Source dataset
uspto-grants-2014_10
Patent number
US08859535B2

Reaction notes

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