Sodium Carbonate → HCID 21947805, compound

HRID 1830095Notes

Reaction equation

HRID 1830095 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14][N:13]3[CH:21]=[CH:22][CH:23]=[C:12]3[CH2:11]2)=[O:9])=[CH:4][C:3]=1[CH3:24].[N:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C(=O)([O-])[O-].[Na+].[Na+].B(O)O>C1(C)C=CC=CC=1.C(O)C.O>[CH3:24][C:3]1[CH:4]=[C:5]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14][N:13]3[CH:21]=[CH:22][CH:23]=[C:12]3[CH2:11]2)=[O:9])[CH:6]=[CH:7][C:2]=1[C:28]1[CH:29]=[CH:30][N:25]=[CH:26][CH:27]=1

Participants

8

Reactant 4

HCID 10340Sodium Carbonate2×HCID 61668Boronic AcidHCID 2734379(Pyridin-4-yl)boronic acidHCID 21947764HCID 21947764, compound

Product 1

HCID 21947805HCID 21947805, compoundYield 23.1%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A suspension of (4-bromo-3-methylphenyl)[10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl]methanone of Step A (1.14 g, 2.9 mmol), pyridine-4-boronic acid (0.368 mg, 2.9 mmol) and sodium carbonate (0.760 g, 7.2 mmol) in a mixture of toluene (30 mL), water (10 mL), and ethanol (5 mL) was sparged with nitrogen for 15 minutes. To this was added tetrakis(triphenylphosphine)palladium(0) (0.027 g) and the mixture was heated to reflux under a static pressure of nitrogen. After 24 hours additional boronic acid (0.128 mg, 1 mmol) and sodium carbonate (0.116 g) were added and the heating was continued for 24 hours. Additional catalyst (0.012 g) was added and heating was continued for another 24 hours. The mixture was partitioned between ethyl acetate and hexane. The water layer was washed twice with ethyl acetate and the combined organic layers were dried over anhydrous magnesium sulfate and stripped to a solid. Flash chromatography of the residue on silica gel eluting with 30% ethyl acetate in hexane provided a solid which was recrystallized from ethyl acetate/hexane to provide the title compound (0.254 g) as tan plates m.p. 208–210° C.

Workup

  1. customwas sparged with nitrogen for 15 minutes
  2. additionTo this was added tetrakis(triphenylphosphine)palladium(0) (0.027 g)
  3. temperaturethe mixture was heated
  4. temperatureto reflux under a static pressure of nitrogen
  5. temperatureheating
  6. waitwas continued for another 24 hours
  7. customThe mixture was partitioned between ethyl acetate and hexane
  8. washThe water layer was washed twice with ethyl acetate
  9. dry with materialthe combined organic layers were dried over anhydrous magnesium sulfate
  10. customFlash chromatography of the residue on silica gel eluting with 30% ethyl acetate in hexane provided a solid which
  11. customwas recrystallized from ethyl acetate/hexane

Sources & evidence

ORD record
ord-3918927d148f40fd85a6fbc7592001cf
Source dataset
uspto-grants-2006_06
Patent number
US07064120B2

Reaction notes

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