Propargyl bromide → 6,6-Dimethyl-8-morpholin-4-yl-9-(3-morpholin-4-yl-prop-1-ynyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

HRID 2275167Notes

Reaction equation

HRID 2275167 reaction equation
Br[C:2]1[C:23]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[CH:22][C:5]2[C:6]([CH3:21])([CH3:20])[C:7]3[NH:8][C:9]4[C:14]([C:15]=3[C:16](=[O:17])[C:4]=2[CH:3]=1)=[CH:13][CH:12]=[C:11]([C:18]#[N:19])[CH:10]=4.Br[CH2:31][C:32]#[CH:33].[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C(=O)([O-])[O-].[Cs+].[Cs+]>O.C(#N)C>[CH3:20][C:6]1([CH3:21])[C:7]2[NH:8][C:9]3[C:14](=[CH:13][CH:12]=[C:11]([C:18]#[N:19])[CH:10]=3)[C:15]=2[C:16](=[O:17])[C:4]2[CH:3]=[C:2]([C:33]#[C:32][CH2:31][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)[C:23]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[CH:22][C:5]1=2

Participants

8

Reactant 5

HCID 7842Propargyl bromideHCID 8083MorpholineHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 66834380HCID 66834380, compound

Product 1

HCID 668343076,6-Dimethyl-8-morpholin-4-yl-9-(3-morpholin-4-yl-prop-1-ynyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To 9-bromo-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound F3-4, 30 mg, 0.067 mmol), 3-bromopropyne (0.01 ml, 0.13 mmol), morpholine (0.029 ml, 0.33 mmol), X-Phos (4.8 mg, 15% mol), PdCl2 (CH3CN)2 (0.9 mg, 5% mol) and cesium carbonate (87 mg, 0.27 mmol), acetonitrile (2 ml) was added and the mixture was stirred at 80° C. for 2 hr. The reaction solution was added to water, and then extracted with dichloromethane. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane/methanol) to obtain the target compound (pale brown solid, 18 mg, 64%).

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. customThe drying agent was removed by filtration
  4. customthe residues obtained
  5. concentrationafter concentration under reduced pressure
  6. customwere purified by silica gel column chromatography (dichloromethane/methanol)
  7. customto obtain the target compound (pale brown solid, 18 mg, 64%)

Sources & evidence

ORD record
ord-84d701097dc5413492679bec832b8870
Source dataset
uspto-grants-2015_09
Patent number
US09126931B2

Reaction notes

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