Diisopropylethylamine → (E)-1-[(1S,4S)-5-(4-Quinolyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]hex-2-en-1-one

HRID 333943Notes

Reaction equation

HRID 333943 reaction equation
Cl.[C@H:2]12[CH2:18][C@H:5]([N:6]([C:8]3[C:17]4[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=4)[N:11]=[CH:10][CH:9]=3)[CH2:7]1)[CH2:4][NH:3]2.C(N(C(C)C)CC)(C)C.[C:28](Cl)(=[O:34])/[CH:29]=[CH:30]/[CH2:31][CH2:32][CH3:33]>ClCCl>[N:11]1[C:12]2[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]([N:6]2[CH2:7][C@@H:2]3[CH2:18][C@H:5]2[CH2:4][N:3]3[C:28](=[O:34])/[CH:29]=[CH:30]/[CH2:31][CH2:32][CH3:33])=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5706484(E)-hex-2-enoyl chlorideHCID 668355714-[(1S,4S)-2,5-Diazabicyclo[2.2.1]heptan-5-yl]quinoline hydrochloride

Product 1

HCID 66835855(E)-1-[(1S,4S)-5-(4-Quinolyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl]hex-2-en-1-oneYield 28%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 4-[(1S,4S)-2,5-diazabicyclo[2.2.1]heptan-5-yl]quinoline hydrochloride (26.2 mg, 0.1 mmol), dissolved in 0.5 ml anhydrous dichloromethane, polymer-supported diisopropylethylamine (80 mg, 3-4 mmol/g) was added followed by (E)-hex-2-enoyl chloride (19.9 mg, 0.15 mmol) dissolved in anhydrous dichloromethane (1 ml). The mixture was shaken at room temperature for 20 minutes, filtered and the filtrate evaporated to dryness under reduced pressure. The raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile) to yield 9 mg of a solid (0.028 mmol, 28%).

Workup

  1. filtrationfiltered
  2. customthe filtrate evaporated to dryness under reduced pressure
  3. customThe raw product was purified by preparative HPLC (gradient of water containing 0.1% ammonia and acetonitrile)

Sources & evidence

ORD record
ord-4dee199dcb1f46eeacecebe808339dd8
Source dataset
uspto-grants-2014_11
Patent number
US08883791B2

Reaction notes

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