Hydrochloric Acid → HCID 70656637, compound

HRID 68972Notes

Reaction equation

HRID 68972 reaction equation
[CH2:1]([N:3]1[C:9](=[O:10])[C:8]([CH3:12])([CH3:11])[C:7](=[O:13])[N:6]([CH3:14])[C:5]2[CH:15]=[C:16]([CH2:19][NH:20][CH2:21][CH2:22][C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)[CH:17]=[CH:18][C:4]1=2)[CH3:2].Br[C:30]1[CH:39]=[CH:38][CH:37]=[C:36]2[C:31]=1[CH:32]=[CH:33][CH:34]=[N:35]2.C(=O)([O-])[O-].[Cs+].[Cs+].[ClH:46]>C(O)C.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].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.O.C1(C)C=CC=CC=1>[ClH:46].[ClH:46].[ClH:46].[CH2:1]([N:3]1[C:9](=[O:10])[C:8]([CH3:12])([CH3:11])[C:7](=[O:13])[N:6]([CH3:14])[C:5]2[CH:15]=[C:16]([CH2:19][N:20]([CH2:21][CH2:22][C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)[C:30]3[CH:39]=[CH:38][CH:37]=[C:36]4[C:31]=3[CH:32]=[CH:33][CH:34]=[N:35]4)[CH:17]=[CH:18][C:4]1=2)[CH3:2]

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 8173215-BromoquinolineHCID 669599071-Ethyl-3,3,5-trimethyl-7-[(2-pyridin-3-yl-ethylamino)methyl]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione

Product 1

HCID 70656637HCID 70656637, compound

Reagents, catalysts & solvents 5

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 702EthanolSolvent2×HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

1-Ethyl-3,3,5-trimethyl-7-{[N-(2-pyridin-3-ylethyl)amino]methyl}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.45 g), 5-bromoquinoline (0.25 g), tris(dibenzylideneacetone)dipalladium (5.4 mg), xantphos (10 mg), and cesium carbonate (0.46 g) were added to toluene (9 ml), and the mixture was heated at 130° C. for 3 days. The reaction liquid was cooled to room temperature. Water was added to the reaction mixture, and stirred for 1 hour, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The filtrate was condensed under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:methanol=85:15). The purified product was condensed under reduced pressure. A 1N-hydrogen chloride in ethanol solution (1 ml) was added to a ethanol solution (5 ml) of the residue, and the liquid was stirred at room temperature, and concentrated under reduced pressure. Ethanol and ether were added to the residue. The precipitated insoluble matter was separated, washed with ether, and dried to give the title compound (0.20 g) as a yellow amorphous.

Workup

  1. customThe reaction liquid
  2. temperaturewas cooled to room temperature
  3. extractionfollowed by extraction with ethyl acetate
  4. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  5. customcondensed under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate:methanol=85:15)
  7. customcondensed under reduced pressure
  8. stirringthe liquid was stirred at room temperature
  9. concentrationconcentrated under reduced pressure
  10. additionEthanol and ether were added to the residue
  11. customThe precipitated insoluble matter was separated
  12. washwashed with ether
  13. customdried

Sources & evidence

ORD record
ord-8b72761e49fe49c5964a76cd074da256
Source dataset
uspto-grants-2014_09
Patent number
US08822453B2

Reaction notes

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