Potassium Phosphate, Tribasic → HCID 89648590, compound

HRID 1773941Notes

Reaction equation

HRID 1773941 reaction equation
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C([O:32][C:33](=[O:54])[CH2:34][C:35]1[CH:40]=[CH:39][C:38]([O:41][CH:42]([CH3:44])[CH3:43])=[C:37](B2OC(C)(C)C(C)(C)O2)[CH:36]=1)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH2:63]([O:70][C:71]([N:73]1[CH2:82][CH2:81][C:80]2[C:75](=[C:76](Cl)[CH:77]=[CH:78][C:79]=2[C:83]#[N:84])[CH2:74]1)=[O:72])[C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:63]([O:70][C:71]([N:73]1[CH2:82][CH2:81][C:80]2[C:75](=[C:76]([C:37]3[CH:36]=[C:35]([CH2:34][C:33]([OH:32])=[O:54])[CH:40]=[CH:39][C:38]=3[O:41][CH:42]([CH3:43])[CH3:44])[CH:77]=[CH:78][C:79]=2[C:83]#[N:84])[CH2:74]1)=[O:72])[C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 89648784HCID 89648784, compoundHCID 89649303HCID 89649303, compound

Product 1

HCID 89648590HCID 89648590, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
100 °C

Procedure

A mixture under N2 of palladium(II) acetate (0.21 mg, 0.9 μmol, 0.01 eq.), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.78 mg, 1.9 mmol, 0.02 eq.), [4-isopropoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid ethyl ester (34 mg, 94.3 μmol, 1.00 eq.) and potassium phosphate (40 mg, 0.19 mmol, 2.00 eq.) in toluene (0.3 mL) and water (0.04 mL) was stirred at r.t. for 2 min. A solution of 8-chloro-5-cyano-3,4-dihydro-1H-isoquinoline-2-carboxylic acid benzyl ester (32.1 mg, 94.3 μmol, 1.00 eq.) in toluene (0.3 mL) was added and the mixture was stirred at 100° C. for 48 hours. The mixture was allowed to cool to r.t., filtered through celite, and concentrated in vacuo. The residue, redissolved in MeCN/H2O (1.6 mL) and formic acid (0.2 mL), was purified by prep. HPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated. The residue was redissolved in DMF (0.45 mL) and 2M aq. NaOH soln. (0.2 mL) was added. The resulting mixture was stirred at r.t. for 1 hour. Formic acid (0.2 mL) was added. The crude mixture was purified by prep. HPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated to give the title compound as a milky oil.

Workup

  1. temperatureto cool to r.t.
  2. filtrationfiltered through celite
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue, redissolved in MeCN/H2O (1.6 mL)
  5. customformic acid (0.2 mL), was purified by prep
  6. customHPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated
  7. dissolutionThe residue was redissolved in DMF (0.45 mL)
  8. addition(0.2 mL) was added
  9. stirringThe resulting mixture was stirred at r.t. for 1 hour
  10. additionFormic acid (0.2 mL) was added
  11. customThe crude mixture was purified by prep
  12. customHPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions) and evaporated

Sources & evidence

ORD record
ord-ef386a5a9c7742b0bb16800caa60e80f
Source dataset
uspto-grants-2016_02
Patent number
US09255090B2

Reaction notes

Loading…