HCID 67541966, compound → HCID 16006724, compound

HRID 2389951Notes

Reaction equation

HRID 2389951 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C:17]3[C:12](=[CH:13][C:14]([O:18][CH2:19][CH2:20][CH2:21][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:15][CH:16]=3)[C@@H:11]3[CH2:28][CH2:29][CH2:30][N:10]3[CH2:9]2)=[CH:4][CH:3]=1.[C:31]([Cu])#[N:32]>CN(C=O)C>[N:22]1([CH2:21][CH2:20][CH2:19][O:18][C:14]2[CH:13]=[C:12]3[C:17]([C@H:8]([C:5]4[CH:6]=[CH:7][C:2]([C:31]#[N:32])=[CH:3][CH:4]=4)[CH2:9][N:10]4[CH2:30][CH2:29][CH2:28][C@@H:11]43)=[CH:16][CH:15]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

4

Reactant 2

HCID 67541966HCID 67541966, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 16006724HCID 16006724, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

To a sealed tube reaction vessel were added cis-6-(4-bromo-phenyl)-9-(3-piperidin-1-yl-propoxy)-1,2,3,5,6,10b-hexahydro-pyrrolo[2,1-a]isoquinoline (0.21 mmol), CuCN (5.2 equiv.), and DMF (1.7 M). The tube was purged with nitrogen, sealed, and heated at 150° C. overnight. The reaction mixture was cooled to rt, diluted with aqueous NaCN, and extracted with diethyl ether. The organic layer was washed with water, satd. aq. NaHCO3, and brine, dried (Na2CO3), and concentrated to give the crude product. Chromatographic purification (NH3 in MeOH/CH2Cl2) followed by reverse-phase HPLC gave the desired product as a mixture with the 6-trans isomer (7% combined yield).

Workup

  1. customThe tube was purged with nitrogen
  2. customsealed
  3. temperatureThe reaction mixture was cooled to rt
  4. additiondiluted with aqueous NaCN
  5. extractionextracted with diethyl ether
  6. washThe organic layer was washed with water
  7. dry with materialaq. NaHCO3, and brine, dried (Na2CO3)
  8. concentrationconcentrated
  9. customto give the crude product
  10. customChromatographic purification (NH3 in MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-6a9b1885f97d47d097897233f60ac7a9
Source dataset
uspto-grants-2012_09
Patent number
US08273762B2

Reaction notes

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