1-Phenylpiperazine → (R)-2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-1-(4-phenylpiperazin-1-yl)propan-1-one

HRID 1876644Notes

Reaction equation

HRID 1876644 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C@H:12]([CH3:16])[C:13]([OH:15])=O)[CH2:7][CH2:6][CH2:5]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:41]1([N:47]2[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([C@H:12]([CH3:16])[C:13]([N:50]1[CH2:51][CH2:52][N:47]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH2:48][CH2:49]1)=[O:15])[CH2:7][CH2:6][CH2:5]2

Participants

7

Reactant 4

HCID 70961-PhenylpiperazineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59465723(R)-2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)propanoic acid

Product 1

HCID 33590812(R)-2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-1-(4-phenylpiperazin-1-yl)propan-1-oneYield 54.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a 0° C. solution of (R)-2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-propanoic acid (16.91 g, 57 mmol) in a (1:1) mixture of methylene dichloride and DMF (150 mL), was added HATU (21.7 g, 57 mmol). The reaction mixture was stirred at this temperature for 10 minutes. To this was added, 1-phenylpiperazine (8.7 mL, 57 mmol), followed by addition of sodium bicarbonate (4.79 g, 57 mmol). Upon completion of addition, the mixture was stirred at 0° C. for 4 hours. The reaction mixture was diluted with 250 mL of methylene chloride and washed with water (1500 mL) and 1M HCl solution (2×250 mL). The organic layer was dried Over magnesium sulfate, filtered, and concentrated. Purification via silica gel chromatography using 20-50% ethyl acetate in hexane gave (R)-2-(6-chloro-3,4-dihydroquinolin-1(2H)-yl)-1-(4-phenylpiperizin-1-yl)propan-1-one as a white solid (11.84 g, 54%). LC/MS (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)), m/z: M+1 obs=384.3; tR=3.59 min.

Workup

  1. additionTo this was added
  2. additionUpon completion of addition
  3. stirringthe mixture was stirred at 0° C. for 4 hours
  4. washwashed with water (1500 mL) and 1M HCl solution (2×250 mL)
  5. dry with materialThe organic layer was dried Over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification via silica gel chromatography

Sources & evidence

ORD record
ord-9f3a96bc998d46f48987d39636946b2e
Source dataset
uspto-grants-2012_11
Patent number
US08309587B2

Reaction notes

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