Phenol → (S)-1-(4-Aminoquinolin-7-ylmethyl)-4-[3-(5-chlorothiophen-2-yl)-allyl]-3-methylpiperazin-2-one

HRID 1432992Notes

Reaction equation

HRID 1432992 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH:20]=[CH:21][C:22]4[S:23][C:24]([Cl:27])=[CH:25][CH:26]=4)[C@@H:15]([CH3:28])[C:14]3=[O:29])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.C1(O)C=CC=CC=1.C([O-])(=O)C.[NH4+:41]>>[NH2:41][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH:20]=[CH:21][C:22]4[S:23][C:24]([Cl:27])=[CH:25][CH:26]=4)[C@@H:15]([CH3:28])[C:14]3=[O:29])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 996PhenolHCID 517165Ammonium AcetateHCID 54504925(S)-1-(4-Chloroquinolin-7-ylmethyl)-4-[3-(5-chlorothiophen-2-yl)-allyl]-3-methylpiperazin-2-one

Product 1

HCID 54343133(S)-1-(4-Aminoquinolin-7-ylmethyl)-4-[3-(5-chlorothiophen-2-yl)-allyl]-3-methylpiperazin-2-oneYield 42.7%

Conditions

Temperature
120 °C

Procedure

(S)-1-(4-Chloroquinolin-7-ylmethyl)-4-[3-(5-chlorothiophen-2-yl)-allyl]-3-methylpiperazin-2-one(0.35 g, 0.82 mmol) is treated with phenol (2 g) and ammonium acetate (0.7 g, 9.1 mmol) and heated to 120° C. in a sealed vessel for 1 hour. Upon cooling, the solution is partitioned between 2 N NaOH and ethyl acetate. The organic layer is separated and washed with fresh 2 N NaOH (3×100 mL) and water. The organic layer is concentrated and the residue is purified by reverse phase HPLC to give the title compound as a white solid (0.15 g, 0.35 mmol). MS (ISP) m/z 427, 429, (M+H), Cl pattern.

Workup

  1. temperatureUpon cooling
  2. customthe solution is partitioned between 2 N NaOH and ethyl acetate
  3. customThe organic layer is separated
  4. washwashed with fresh 2 N NaOH (3×100 mL) and water
  5. concentrationThe organic layer is concentrated
  6. customthe residue is purified by reverse phase HPLC

Sources & evidence

ORD record
ord-ba22ead2c6304d2788c8cbc278a6c3f3
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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