Sodium Carbonate → 2'-Amino-2-methoxy-1,1'-dimethyl-7-pyridin-3-yl-10,11-dihydrospiro[dibenzo[a,d][7]annulene-5,4'-imidazol]-5'(1'H)-one

HRID 730181Notes

Reaction equation

HRID 730181 reaction equation
[NH2:1][C:2]1[N:3]([CH3:25])[C:4](=[O:24])[C:5]2([C:12]3[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[CH:16][C:11]=3[CH2:10][CH2:9][C:8]3[CH:19]=[CH:20][C:21](Br)=[CH:22][C:7]2=3)[N:6]=1.[N:26]1[CH:31]=[CH:30][CH:29]=[C:28](B(O)O)[CH:27]=1.[C:35]([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[NH2:1][C:2]1[N:3]([CH3:25])[C:4](=[O:24])[C:5]2([C:12]3[CH:13]=[CH:14][C:15]([O:17][CH3:18])=[C:16]([CH3:35])[C:11]=3[CH2:10][CH2:9][C:8]3[CH:19]=[CH:20][C:21]([C:28]4[CH:27]=[N:26][CH:31]=[CH:30][CH:29]=4)=[CH:22][C:7]2=3)[N:6]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 249832682'-Amino-2-methoxy-1'-methyl-7-bromo-10,11-dihydrospiro[dibenzo[a,d][7]-annulene-5,4'-imidazol]-5'(1'H)-one

Product 1

HCID 249832692'-Amino-2-methoxy-1,1'-dimethyl-7-pyridin-3-yl-10,11-dihydrospiro[dibenzo[a,d][7]annulene-5,4'-imidazol]-5'(1'H)-oneYield 44%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2′-amino-2-methoxy-1′-methyl-7-bromo-10,11-dihydrospiro[dibenzo[a,d][7]annulene-5,4′-imidazol]-5′(1′H)-one (0.130 g; 0.314 mmol), dioxane (5 mL, de-oxygenated), 3-pyridineboronic acid (77.1 mg; 0.628 mmol) and 2.0 N Na2CO3 solution (0.63 mL; 4.0 eq.) was stirred at reflux temperature for one hour, cooled to ambient temperature and concentrated in vacuo. The resultant residue was partitioned in chloroform and water. The organic phase was dried over sodium sulfate, filtered, and evaporated. This residue was purified by HPLC with a Phenomenex CN column using a solvent system consisting of A) hexane and B) dichloromethane/methanol (4:1). A gradient starting at 50% B and increasing to 100% B was used for purification. The purified solid was crystallized from hot ethyl acetate and hexane to yield the title compound as tan crystals, 57 mg (44% yield), mp 235-9° C.; identified by NMR and mass spectral analyses. MS (ES) m/z 413.15 [M+H]+.

Workup

  1. temperatureat reflux temperature for one hour
  2. concentrationconcentrated in vacuo
  3. customThe resultant residue was partitioned in chloroform
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThis residue was purified by HPLC with a Phenomenex CN column
  8. temperatureincreasing to 100% B
  9. customwas used for purification
  10. customThe purified solid was crystallized from hot ethyl acetate and hexane

Sources & evidence

ORD record
ord-6c3eeaf512e24100af6aa848214abe56
Source dataset
uspto-grants-2009_09
Patent number
US07582667B2

Reaction notes

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