2,4-Dimethoxybenzylamine → 3-Chloro-7-[[(2,4-dimethoxyphenyl)methyl]amino]-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one

HRID 222259Notes

Reaction equation

HRID 222259 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[CH:16]=[CH:15][C:9]3=[N:10][CH:11]=[C:12]([Cl:14])[CH:13]=[C:8]3[C:7](=[O:17])[C:6]=2[CH:18]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+].[CH3:71][O:72][C:73]1[CH:80]=[C:79]([O:81][CH3:82])[CH:78]=[CH:77][C:74]=1[CH2:75][NH2:76]>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.O1CCOCC1>[Cl:14][C:12]1[CH:13]=[C:8]2[C:7](=[O:17])[C:6]3[CH:18]=[C:2]([NH:76][CH2:75][C:74]4[CH:77]=[CH:78][C:79]([O:81][CH3:82])=[CH:80][C:73]=4[O:72][CH3:71])[CH:3]=[CH:4][C:5]=3[CH:16]=[CH:15][C:9]2=[N:10][CH:11]=1

Participants

7

Reactant 4

HCID 5972502,4-DimethoxybenzylamineHCID 634876Binap, (A+-)-HCID 159808187-Bromo-3-chloro-5H-benzo[4,5]cyclohepta[1,2-B]pyridin-5-oneHCID 23676156Sodium t-butoxide

Product 1

HCID 159808203-Chloro-7-[[(2,4-dimethoxyphenyl)methyl]amino]-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

7-bromo-3-chloro-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (3.0 g, 9.40 mmol), tris(dibenzylideneacetone) dipalladium (0) (Pd2(dba3)) (43 mg, 0.047 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binapthyl (BINAP) (88 mg, 0.141 mmol), and sodium tert-butoxide (1.08 g, 11.3 mmol) were combined in a dry flask through which argon was purged. The flask was charged with 100 mL of dry dioxane, 2,4-dimethoxybenzylamine (1.41 mL, 9.40 mmol) was added, and the mixture was sparged with argon for 5 minutes. The reaction was heated to 100° C. and stirred under argon. After 2 h the reaction was concentrated and dissolved in 400 ml of ethyl acetate and washed with 100 mL of saturated aqueous ammonium chloride solution. The organic layer was separated, dried with magnesium sulfate, filtered, and concentrated. The resultant solids were slurried in 50 mL hot methanol, then allowed to cool to ambient temperature. The solids were filtered and dried to afford the title compound. LRMS (APCI) calculated for C23H20ClN2O3 [M+H]+, 407.1; found 407.1.

Workup

  1. customwas purged
  2. additionwas added
  3. customthe mixture was sparged with argon for 5 minutes
  4. concentrationAfter 2 h the reaction was concentrated
  5. dissolutiondissolved in 400 ml of ethyl acetate
  6. washwashed with 100 mL of saturated aqueous ammonium chloride solution
  7. customThe organic layer was separated
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. temperatureto cool to ambient temperature
  12. filtrationThe solids were filtered
  13. customdried

Sources & evidence

ORD record
ord-07f77f4fa8a346e6911bc8e6feb5b2b1
Source dataset
uspto-grants-2012_06
Patent number
US08207186B2

Reaction notes

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