Dichloromethane → (E)-4-chloro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one

HRID 333950Notes

Reaction equation

HRID 333950 reaction equation
CN(C([O:8]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:25](N([CH:31]([CH3:33])[CH3:32])CC)([CH3:27])[CH3:26].[N:34]1([C:40]2[C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[N:43]=[CH:42][CH:41]=2)[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1.Cl[CH2:51][Cl:52]>>[Cl:52][CH2:51]/[CH:33]=[CH:31]/[C:32]([N:37]1[CH2:38][CH2:39][N:34]([C:40]2[C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[N:43]=[CH:42][CH:41]=2)[CH2:35][CH2:36]1)=[O:8].[Cl:52][CH2:51]/[CH:26]=[CH:25]\[C:27]([N:37]1[CH2:38][CH2:39][N:34]([C:40]2[C:49]3[C:44](=[CH:45][CH:46]=[CH:47][CH:48]=3)[N:43]=[CH:42][CH:41]=2)[CH2:35][CH2:36]1)=[O:8]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 81531Diisopropylethylamine2×HCID 15343864-Piperazin-1-yl-quinolineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 2

HCID 66835944(Z)-4-chloro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-oneYield 15%HCID 66837142(E)-4-chloro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-oneYield 33%

Procedure

The mixture of (E)- and (Z)-4-chlorobut-2-enoic acid (750 μl of the solution from step A, 0.19 mmol) together with HATU (72 mg, 0.19 mmol) and diisopropylethylamine (21.6 μl, 0.375 mmol) was stirred at room temperature for 15 minutes. 4-piperazin-1-ylquinoline (39.9 mg, 0.19 mmol) and diisopropylethylamine (10.8 μl) were added and stirring was continued for one hour. The mixture was diluted with dichloromethane, washed with 5% sodium bicarbonate solution, water, evaporated to dryness under reduced pressure and purified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile) to yield 20 mg (E)-4-chloro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one (0.063 mmol, 33%) and 9 mg (Z)-4-chloro-1-[4-(4-quinolyl)piperazin-1-yl]but-2-en-1-one (0.029 mmol, 15%).

Workup

  1. stirringstirring
  2. waitwas continued for one hour
  3. washwashed with 5% sodium bicarbonate solution, water
  4. customevaporated to dryness under reduced pressure
  5. custompurified by preparative HPLC (gradient of water containing 0.1% NH3 and acetonitrile)

Sources & evidence

ORD record
ord-98065993b97641dca27359660aa0cd3c
Source dataset
uspto-grants-2014_11
Patent number
US08883791B2

Reaction notes

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