1-Isopropylpiperazine → N-[3-(4-isopropylpiperazin-1-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]methanesulfonamide

HRID 1987111Notes

Reaction equation

HRID 1987111 reaction equation
Cl[C:2]1[CH:3]=[C:4]2[C:12](=[O:13])[C:11]3[CH:14]=[C:15]([NH:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH:16]=[CH:17][C:10]=3[CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1.[CH:23]([N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)([CH3:25])[CH3:24].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:23]([N:26]1[CH2:31][CH2:30][N:29]([C:2]2[CH:3]=[C:4]3[C:12](=[O:13])[C:11]4[CH:14]=[C:15]([NH:18][S:19]([CH3:22])(=[O:21])=[O:20])[CH:16]=[CH:17][C:10]=4[CH:9]=[CH:8][C:5]3=[N:6][CH:7]=2)[CH2:28][CH2:27]1)([CH3:25])[CH3:24]

Participants

6

Reactant 4

HCID 780131-IsopropylpiperazineHCID 634876Binap, (A+-)-HCID 15980822N-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)methanesulfonamideHCID 23676156Sodium t-butoxide

Product 1

HCID 16035632N-[3-(4-isopropylpiperazin-1-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]methanesulfonamide

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
105 °C

Procedure

N-(3-chloro-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl)methanesulfonamide (0.050 g, 0.15 mmol), isopropylpiperazine (0.038 g, 0.30 mmol), Pd2(dba)3 (1.5 mg, 0.0015 mmol), BINAP (3.0 mg, 0.0045 mmol), and sodium tert-butoxide (0.043 g, 0.45 mmol) were added to a dry flask through which argon was purged. 3.0 mL dry dioxane was added and argon was bubbled through the solution for 5 minutes. The reaction was stirred and heated to 105° C. After 12 hours, the reaction mixture was poured into 100 mL ethyl acetate, 100 mL water, and 25 mL saturated ammonium chloride. The organic layer was separated, dried with magnesium sulfate, filtered, concentrated, and purified by reverse phase HPLC (20-100% acetonitrile/water gradient, 0.1% trifluoroacetic acid modifier) to afford the title compound.

Workup

  1. customwas purged
  2. addition3.0 mL dry dioxane was added
  3. customargon was bubbled through the solution for 5 minutes
  4. additionthe reaction mixture was poured into 100 mL ethyl acetate, 100 mL water, and 25 mL saturated ammonium chloride
  5. customThe organic layer was separated
  6. dry with materialdried with magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified by reverse phase HPLC (20-100% acetonitrile/water gradient, 0.1% trifluoroacetic acid modifier)

Sources & evidence

ORD record
ord-fffbc30b7c754d60b741fdcc50a950ea
Source dataset
uspto-grants-2009_06
Patent number
US07550478B2

Reaction notes

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