Sodium Carbonate → (2-Chloro-4-thiophen-3-yl-phenyl)-(5,11-dihydro-pyrido[2,3-b][1,5] benzodiazepin-10-yl)-methanone

HRID 378898Notes

Reaction equation

HRID 378898 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[C:20]3[NH:19][C:18]4[N:21]=[CH:22][CH:23]=[CH:24][C:17]=4[CH2:16][NH:15][C:14]=3[CH:13]=[CH:12][CH:11]=2)=[O:9])=[C:4]([Cl:25])[CH:3]=1.[S:26]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27]1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:25][C:4]1[CH:3]=[C:2]([C:28]2[CH:29]=[CH:30][S:26][CH:27]=2)[CH:7]=[CH:6][C:5]=1[C:8]([C:10]1[C:20]2[NH:19][C:18]3[N:21]=[CH:22][CH:23]=[CH:24][C:17]=3[CH2:16][NH:15][C:14]=2[CH:13]=[CH:12][CH:11]=1)=[O:9]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 581760Thiophene-3-boronic acidHCID 21696873(4-Bromo-2-chloro-phenyl)-(5,11-dihydro-pyrido [2,3-b][1,5] benzodiazepin-10-yl)-methanone

Product 1

HCID 21696871(2-Chloro-4-thiophen-3-yl-phenyl)-(5,11-dihydro-pyrido[2,3-b][1,5] benzodiazepin-10-yl)-methanoneYield 46.7%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a solution of the (4-bromo-2-chloro-phenyl)-(5,11-dihydro-pyrido[2,3-b][1,5] benzodiazepin-10-yl)-methanone of Example 7, Step A (0.5 g, 1.23 mmol), thiophene-3-boronic acid (0.158 g, 1.23 mmol) and sodium carbonate (0.568 g, 5.36 mmol) in toluene (20 mL), ethanol (10 mL) and water (10 mL) under nitrogen was added the tetrakis (triphenylphosphine) palladium(0) catalyst (0.06 g, 0.052 mmol). The reaction was heated at reflux for 20 hours, cooled, and filtered through Celite, which was then rinsed with ethyl acetate. The organic layer was washed with water, dried over sodium sulfate and evaporated to dryness. The residue (blue-green oil) was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with 25% ethyl acetate in hexane yielded a foam (0.24 g) which was triturated with diethyl ether-hexane to provide the title compound as a white solid, m.p. 125-130° C.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 20 hours
  3. temperaturecooled
  4. filtrationfiltered through Celite, which
  5. washwas then rinsed with ethyl acetate
  6. washThe organic layer was washed with water
  7. dry with materialdried over sodium sulfate
  8. customevaporated to dryness
  9. dissolutionThe residue (blue-green oil) was dissolved in dichloromethane
  10. customabsorbed onto a silica Merck-60 flash column
  11. washElution with 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-256bb122c8b84e48a20faac952684de0
Source dataset
uspto-grants-2001_10
Patent number
US06297234B1

Reaction notes

Loading…