Pyridine → 2-[5-(4-t-Butoxycarbonylhexahydro-1,4-diazepin-1-yl)pyrazin-2-ylcarbonylamino]-5-fluoro-N-(5-chloropyridin-2-yl)-benzamide

HRID 1372875Notes

Reaction equation

HRID 1372875 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]([C:8]([NH:10][C:11]2[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:12]=2[C:13]([NH:15][C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][N:17]=2)=[O:14])=[O:9])=[N:6][CH:7]=1.[C:28]([N:35]1[CH2:41][CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].N1C=CC=CC=1.CCOCC>CS(C)=O.C(OCC)(=O)C>[C:31]([O:30][C:28]([N:35]1[CH2:41][CH2:40][CH2:39][N:38]([C:2]2[N:3]=[CH:4][C:5]([C:8]([NH:10][C:11]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:12]=3[C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][N:17]=3)=[O:14])=[O:9])=[N:6][CH:7]=2)[CH2:37][CH2:36]1)=[O:29])([CH3:34])([CH3:32])[CH3:33]

Participants

7

Reactant 4

HCID 1049PyridineHCID 3283Diethyl EtherHCID 2756058Tert-butyl 1,4-diazepane-1-carboxylateHCID 111539812-(5-chloropyrazin-2-ylcarbonylamino)-5-fluoro-N-(5-chloropyridin-2-yl)benzamide

Product 1

HCID 111806062-[5-(4-t-Butoxycarbonylhexahydro-1,4-diazepin-1-yl)pyrazin-2-ylcarbonylamino]-5-fluoro-N-(5-chloropyridin-2-yl)-benzamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution (or suspension) of 2-(5-chloropyrazin-2-ylcarbonylamino)-5-fluoro-N-(5-chloropyridin-2-yl)benzamide (Intermediate A-1, 10 g, 24.62 mmol) in DMSO (30 mL) was added 1-Boc-hexahydro-1,4-diazepine (9.86 g, 49.23 mmol) and pyridine (2.4 mL, 30 mmol). The reaction mixture was stirred for one hour at room temperature before it was heated in a sealed tube at 75–80° C. for 18 h. The mixture was cooled to room temperature, diluted with ethyl acetate (800 mL), washed with saturated aqueous citric acid solution (3×200 mL), water (200 mL), saturated sodium bicarbonate solution (2×200 mL), and dried over magnesium sulfate. Activated charcoal (3 g) was added to decolorize the product. Evaporation of the solvent under vacuum provided 13.9 g of crude product. Ether (150 mL) was added to this solid, the mixture was sonicated 20 min, and the solids were filtered and dried under vacuum to afford the title compound as a solid which was analytically pure. Yield=12.6 g

Workup

  1. temperaturewas heated in a sealed tube at 75–80° C. for 18 h
  2. temperatureThe mixture was cooled to room temperature
  3. washwashed with saturated aqueous citric acid solution (3×200 mL), water (200 mL), saturated sodium bicarbonate solution (2×200 mL)
  4. dry with materialdried over magnesium sulfate
  5. additionActivated charcoal (3 g) was added
  6. customEvaporation of the solvent under vacuum
  7. customprovided 13.9 g of crude product
  8. customthe mixture was sonicated 20 min
  9. filtrationthe solids were filtered
  10. customdried under vacuum

Sources & evidence

ORD record
ord-2890b73e47044a878b01d6d3444c9540
Source dataset
uspto-grants-2007_01
Patent number
US07160878B2

Reaction notes

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