Sodium Carbonate → HCID 60170439, compound

HRID 1365510Notes

Reaction equation

HRID 1365510 reaction equation
BrC1C=CC(C(NC(NC2CCCC2)=O)(C2C=C(C(F)(F)F)C=C(F)C=2)CC2C=CC=CC=2)=NC=1.C([O-])([O-])=O.[Na+].[Na+].[C:42]([C:44]1[CH:45]=[CH:46][C:47]([C@:50]([NH:69][C:70]([NH:72][CH:73]2[CH2:77][CH2:76][CH2:75][CH2:74]2)=[O:71])([C:58]2[CH:63]=[C:62]([C:64]([F:67])([F:66])[F:65])[CH:61]=[C:60]([F:68])[CH:59]=2)[CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)=[N:48][CH:49]=1)#[N:43]>CC(N(C)C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:42]([C:44]1[CH:45]=[CH:46][C:47]([C@@:50]([NH:69][C:70]([NH:72][CH:73]2[CH2:74][CH2:75][CH2:76][CH2:77]2)=[O:71])([C:58]2[CH:63]=[C:62]([C:64]([F:65])([F:66])[F:67])[CH:61]=[C:60]([F:68])[CH:59]=2)[CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)=[N:48][CH:49]=1)#[N:43]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 58921324HCID 58921324, compoundHCID 66934505HCID 66934505, compound

Product 1

HCID 60170439HCID 60170439, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
120 °C

Procedure

1-(1-(5-Bromopyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-cyclopentylurea (100 mg, 0.18 mmol, prepared in a similar manner as described in Example 1), K4Fe(CN)6 (45 mg, 0.107 mmol), Pd(OAc)2 (catalytic amount, spatula tip), and Na2CO3 (31 mg, 0.29 mmol) were stirred in DMAC (0.4 mL) at room temperature. Argon was purged several times. The reaction mixture was stirred and heated at 120° C. for 6 h. After cooling, EtOAc was added. The reaction mixture was filtered through Celite and the filtrate was washed with H2O, 5% NH4OH, dried (MgSO4), filtered, and concentrated to dryness. The crude reaction mixture was purified by flash chromatography (silica gel, hexanes/EtOAc, came out 50% EtOAc). The reaction mixture was then further purified by reverse phase HPLC (20%-100% CH3CN in H2O with 0.1 TFA in a 18 min run, came out at 13.38 to 13.88 min) to give pure racemic mixture of (R)-1-(1-(5-cyanopyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-cyclopentylurea and (S)-1-(1-(5-cyanopyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-phenylethyl)-3-cyclopentylurea as white solids (16 mg, yield: 18%). LC-MS ESI (10-90% MeOH in H2O with 10 mM NH4Cl in a 4-min run), retention time=3.93 min, 494.9 (M−H);

Workup

  1. customArgon was purged several times
  2. temperatureAfter cooling
  3. additionEtOAc was added
  4. filtrationThe reaction mixture was filtered through Celite
  5. washthe filtrate was washed with H2O, 5% NH4OH
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated to dryness
  9. customThe crude reaction mixture
  10. customwas purified by flash chromatography (silica gel, hexanes/EtOAc
  11. customThe reaction mixture was then further purified by reverse phase HPLC (20%-100% CH3CN in H2O with 0.1 TFA in a 18 min
  12. custom) to give pure

Sources & evidence

ORD record
ord-91c94455a9a04728b282a82cd6b4734b
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

Loading…