Naphthalene → 2-Ethyl-9-methyl-13-(3-phenylpropyl)-2,4,9,15-tetraazatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-10-one

HRID 724963Notes

Reaction equation

HRID 724963 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[Li].BrCCCC1C=CC=CC=1.[CH2:22]([N:24]1[C:30]2[N:31]=[CH:32]C(I)=[CH:34][C:29]=2[C:28](=[O:36])[N:27]([CH3:37])[C:26]2[CH:38]=[CH:39][CH:40]=[N:41][C:25]1=2)[CH3:23]>O1CCCC1.[Cl-].[Zn+2].[Cl-].[Zn].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:22]([N:24]1[C:30]2[N:31]=[CH:32][C:6]([CH2:7][CH2:8][CH2:9][C:10]3[CH:1]=[CH:2][CH:3]=[CH:4][CH:5]=3)=[CH:34][C:29]=2[C:28](=[O:36])[N:27]([CH3:37])[C:26]2[CH:38]=[CH:39][CH:40]=[N:41][C:25]1=2)[CH3:23]

Participants

9

Reactant 4

HCID 931NaphthaleneHCID 12503(3-Bromopropyl)benzeneHCID 3028194LithiumHCID 10547779HCID 10547779, compound

Product 1

HCID 4707262-Ethyl-9-methyl-13-(3-phenylpropyl)-2,4,9,15-tetraazatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-10-oneYield 7.4%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of naphthalene (0.65 g, 5.07 mmol) in 2 mL of tetrahydrofuran was added to lithium wire (35 mg, 5.04 mmol), and the mixture was stirred overnight at room temperature under argon. A solution of zinc chloride in tetrahydrofuran (0.5M, 5.25 mL, 2.63 mmol) was then added. After 20 min, 1-bromo-3-phenylpropane (0.18 mL, 1.15 mmol) was added, and the reaction mixture was stirred at room temperature for 4.5 hours. Unreacted zinc was allowed to settle, and the supernatant was added by cannula to a solution of 5,11-dihydro-11-ethyl-8-iodo-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (0.22 g, 0.58 mmol) and tetrakis(triphenylphosphine)palladium(0) (70 mg, 0.06 mmol) in 3 mL of tetrahydrofuran. The reaction mixture was allowed to stir overnight at room temperature under argon. The reaction was quenched by the addition of saturated aqueous ammonium chloride, and the product was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over magnesium sulfate, and concentrated. Purification by flash chromatography, eluting with ethyl acetate/dichloromethane, and recrystallization from ethyl acetate/hexanes afforded 16 mg of the title compound as off-white crystals, m.p. 100°-102° C.

Workup

  1. waitAfter 20 min
  2. stirringthe reaction mixture was stirred at room temperature for 4.5 hours
  3. stirringto stir overnight at room temperature under argon
  4. customThe reaction was quenched by the addition of saturated aqueous ammonium chloride
  5. extractionthe product was extracted with ethyl acetate
  6. washThe organic layer was washed with saturated aqueous sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customPurification by flash chromatography
  10. washeluting with ethyl acetate/dichloromethane, and recrystallization from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-3280a3dd59c141bd8b22e869fc0d9c37
Source dataset
uspto-grants-1998_01
Patent number
US05705499

Reaction notes

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