Cesium carbonate → HCID 68926468, compound

HRID 1437426Notes

Reaction equation

HRID 1437426 reaction equation
Br[C:2]1[C:3]([F:20])=[CH:4][C:5]2[N:9]=[CH:8][N:7]([C@H:10]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH3:11])[C:6]=2[CH:19]=1.C(OC([N:28]1[C:32]([NH2:33])=[CH:31][C:30]([CH:34]2[CH2:36][CH2:35]2)=[N:29]1)=O)(C)(C)C.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+].[NH4+].[Cl-]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CCOC(C)=O>[CH:34]1([C:30]2[NH:29][N:28]=[C:32]([NH:33][C:2]3[C:3]([F:20])=[CH:4][C:5]4[N:9]=[CH:8][N:7]([C@H:10]([C:12]5[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=5)[CH3:11])[C:6]=4[CH:19]=3)[CH:31]=2)[CH2:36][CH2:35]1

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 11356513tert-butyl 5-amino-3-cyclopropyl-1H-pyrazole-1-carboxylateHCID 68522609HCID 68522609, compound

Product 1

HCID 68926468HCID 68926468, compoundYield 60.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of (S)-6-bromo-5-fluoro-1-(1-(4-fluorophenyl)ethyl)-1H-benzo[d]imidazole (Method 44; 0.200 g, 0.59 mmol), 5-amino-3-cyclopropyl-1H-pyrazole-1-carboxylic acid tert-butyl ester (0.166 g, 0.741 mmol), Pd2 dba3 (0.011 g, 0.012 mmol), Xantphos (0.021 g, 0.036 mmol), and Cs2CO3 (0.483 g, 1.48 mmol) in toluene (5 ml) was heated at reflux for 18 hrs. To this was added 10 ml of EtOAc and saturated NH4Cl solution (10 ml). The organic layer was separated, washed with brine (10 ml), dried over Na2SO4, and concentrated under reduced pressure. The resulted residue was dissolved in the mixture of DCM:TFA (3:1 v/v, 4 ml), stirred at 25° C. for 2 hrs, concentrated, and treated carefully with saturated NaHCO3 solution (5 ml). The aqueous layer was extracted with DCM (10 ml), dried over Na2SO4, concentrated under reduced pressure, and purified by column chromatography (EtOAc) to give the title compound as a white solid (0.135 g, 60%). NMR (400 MHz) 11.71 (br, 1H), 8.30 (s, 1H), 8.04 (rb, 1H), 7.91 (s, 1H), 7.40 (d, J=12 Hz, 1H), 7.31 (m, 2H), 7.18 (m, 2H), 5.67 (m, 1H), 5.53 (s, 1H), 1.93 (br, 3H), 1.84 (m, 1H), 0.92 (m, 2H), 0.65 (m, 2H). MS: Calcd.: 379; Found: [M+H]+ 380.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 18 hrs
  3. customThe organic layer was separated
  4. washwashed with brine (10 ml)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. dissolutionThe resulted residue was dissolved in the mixture of DCM:TFA (3:1 v/v, 4 ml)
  8. concentrationconcentrated
  9. additiontreated carefully with saturated NaHCO3 solution (5 ml)
  10. extractionThe aqueous layer was extracted with DCM (10 ml)
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated under reduced pressure
  13. custompurified by column chromatography (EtOAc)

Sources & evidence

ORD record
ord-ed9909cbf8764193bdfe7e251f716812
Source dataset
uspto-grants-2009_11
Patent number
US07622482B2

Reaction notes

Loading…