Sodium Carbonate → HCID 86621806, compound

HRID 729472Notes

Reaction equation

HRID 729472 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][C:12]([N:15]3[CH2:20][CH2:19][CH:18]([O:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[C:28]([F:31])([F:30])[F:29])[CH2:17][CH2:16]3)=[N:13][CH:14]=2)O1.Br[C:34]1[CH:35]=[N:36][N:37]([CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH:38]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C=O)C>[F:29][C:28]([F:30])([F:31])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[O:21][CH:18]1[CH2:17][CH2:16][N:15]([C:12]2[N:13]=[CH:14][C:9]([C:34]3[CH:35]=[N:36][N:37]([CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH:38]=3)=[CH:10][N:11]=2)[CH2:20][CH2:19]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 7017475(4-Bromo-pyrazol-1-yl)-acetic acid ethyl esterHCID 69065180HCID 69065180, compound

Product 1

HCID 86621806HCID 86621806, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

Into a 50-mL round-bottom flask equipped with a magnetic stirbar and reflux condenser was added 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}pyrimidine (311 mg, 1.35 mmol), ethyl (4-bromo-1H-pyrazol-1-yl)acetate (400 mg, 0.89 mmol), PdCl2(dppf) (36 mg, 0.05 mmol), 2 M aqueous sodium carbonate solution (0.89 mL, 1.8 mmol) and DMF (4 mL). The resulting suspension was degassed under nitrogen for 20 min and then heated in the microwave to 120° C. for 20 min. The mixture was poured into a 125-mL separatory funnel containing a saturated aqueous KH2PO4 solution (50 mL) and the mixture was extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered and the solvent was evaporated under reduced pressure. Purification by column chromatography through silica gel, eluting with 30% EtOAc in hexanes to 70% EtOAc in hexanes as a gradient gave the title compound as a white solid. MS (ESI, Q+) m/z 476 (M+1).

Workup

  1. customInto a 50-mL round-bottom flask equipped with a magnetic stirbar
  2. temperaturereflux condenser
  3. customThe resulting suspension was degassed under nitrogen for 20 min
  4. additionThe mixture was poured into a 125-mL separatory funnel
  5. additioncontaining a saturated aqueous KH2PO4 solution (50 mL)
  6. extractionthe mixture was extracted with ethyl acetate (3×30 mL)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customthe solvent was evaporated under reduced pressure
  11. customPurification by column chromatography through silica gel
  12. washeluting with 30% EtOAc in hexanes to 70% EtOAc in hexanes as a gradient

Sources & evidence

ORD record
ord-807c118c2ec14c3f874e068930c585a6
Source dataset
uspto-grants-2009_09
Patent number
US07582633B2

Reaction notes

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