5-Chloro-2-ethyl-9-methyl-13-(2-phenylethyl)-2,4,9,15-tetraazatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-10-one → 2-ethyl-9-methyl-13-(2-phenylethyl)-5-(1H-pyrrol-2-yl)-2,4,9,15-tetraazatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3(8),4,6,11,13-hexaen-10-one

HRID 724945

Reaction equation

HRID 724945 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([CH3:28])[C:7](=[O:27])[C:8]3[CH:18]=[C:17]([CH2:19][CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH:16]=[N:15][C:9]=3[N:10]([CH2:13][CH3:14])[C:11]=2[N:12]=1.C([O-])(=O)C.[K+].C(OC([N:41]1[CH:45]=[CH:44][CH:43]=[CH:42]1)=O)(C)(C)C>CN(C)C=O.O.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>[CH2:13]([N:10]1[C:9]2[N:15]=[CH:16][C:17]([CH2:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:18][C:8]=2[C:7](=[O:27])[N:6]([CH3:28])[C:5]2[CH:4]=[CH:3][C:2]([C:42]3[NH:41][CH:45]=[CH:44][CH:43]=3)=[N:12][C:11]1=2)[CH3:14]

Participants

7

Reactant 3

HCID 4706675-Chloro-2-ethyl-9-methyl-13-(2-phenylethyl)-2,4,9,15-tetraazatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3,5,7,12,14-hexaen-10-oneHCID 517044Potassium Acetate2×HCID 643494tert-butyl 1H-pyrrole-1-carboxylate2×

Product 1

HCID 4707432-ethyl-9-methyl-13-(2-phenylethyl)-5-(1H-pyrrol-2-yl)-2,4,9,15-tetraazatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3(8),4,6,11,13-hexaen-10-oneYield 18.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
125 °C

Procedure

A mixture containing 2-chloro-5,11-dihydro-11-ethyl-5-methyl-8-(2-phenylethyl)-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one (0.10 g, 0.26 mmol), potassium acetate (0.05 g, 0.51 mmol), N-(tert-butyloxycarbonyl)pyrrole (0.078 g, 0.47 mmol), and tetrakis(triphenylphosphine)palladium(0) (20 mg, 0.02 mmol) in 2 mL of N,N-dimethylformamide was heated in a sealed tube at 125° C. for 10 hours. Additional potassium acetate (50 mg), N-(tert-butyloxycarbonyl)pyrrole (0.08 g), and tetrakis(triphenylphosphine)palladium(0) (15 mg) were added, and the reaction mixture was heated at 140° C. for an additional 8 hours. The reaction mixture was diluted with water and 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/hexanes, provided 20 mg of the title compound, as a foam.

Workup

  1. temperaturethe reaction mixture was heated at 140° C. for an additional 8 hours
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customPurification by flash chromatography
  7. washeluting with ethyl acetate/hexanes

Sources & evidence

ORD record
ord-b2a53aa7ba3043d680c5ca2f203e13b6
Source dataset
uspto-grants-1998_01
Patent number
US05705499

Linked notes

Loading…