Cesium carbonate → HCID 67072585, compound

HRID 1948173Notes

Reaction equation

HRID 1948173 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[CH:5]2.[CH2:12]([O:19][C:20](=[O:33])[NH:21][CH:22]([C:25]1([CH3:32])[CH2:30][CH2:29][CH:28]([NH2:31])[CH2:27][CH2:26]1)[CH2:23][CH3:24])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:12]([O:19][C:20](=[O:33])[NH:21][CH:22]([C:25]1([CH3:32])[CH2:30][CH2:29][CH:28]([NH:31][C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[CH:8]=[N:7][CH:6]=[CH:5]3)[CH2:27][CH2:26]1)[CH2:23][CH3:24])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 3136816-BromoisoquinolineHCID 634876Binap, (A+-)-HCID 67072976HCID 67072976, compound

Product 1

HCID 67072585HCID 67072585, compoundYield 31.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

In 2 mL of absolute toluene were dissolved 100 mg (481 μmol) of 6-bromo-isoquinoline, 176 mg (577 μmol) of [1-(4-amino-1-methyl-cyclohexyl)-propyl]-carbamic acid benzyl ester (79), and 235 mg (721 μmol) of cesium carbonate. The solution was degassed twice, then 3.24 mg (14.4 μmol) of palladium acetate and 13.5 mg (21.6 μmol) of 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl were added and the reaction mixture was heated to 100° C. until complete conversion could be observed. The mixture was evaporated, the residue dissolved in 50 mL of dichloromethane and washed twice with 50 mL of saturated aqueous sodium bicarbonate solution. The organic phase was dried over magnesium sulphate, filtered, concentrated and purified by silica gel chromatography (dichloromethane:methanol) to give 66 mg of the pure desired product. Rt=1.32 min (Method O). Detected mass: 432.3 (M+H+).

Workup

  1. customThe solution was degassed twice
  2. customThe mixture was evaporated
  3. dissolutionthe residue dissolved in 50 mL of dichloromethane
  4. washwashed twice with 50 mL of saturated aqueous sodium bicarbonate solution
  5. dry with materialThe organic phase was dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified by silica gel chromatography (dichloromethane:methanol)

Sources & evidence

ORD record
ord-2c0785fc78b84027b34f3d6f33b4bc06
Source dataset
uspto-grants-2013_03
Patent number
US08399482B2

Reaction notes

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