Phenol → (S)-1-(4-Aminoquinolin-7-ylmethyl)-4-[3-(4-bromothiophen-2-yl)acryloyl]-3-methyl-piperazin-2-one

HRID 1432994Notes

Reaction equation

HRID 1432994 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]([C:19](=[O:28])[CH:20]=[CH:21][C:22]4[S:23][CH:24]=[C:25]([Br:27])[CH:26]=4)[C@@H:15]([CH3:29])[C:14]3=[O:30])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.C1(O)C=CC=CC=1.C([O-])(=O)C.[NH4+:42]>>[NH2:42][C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:19](=[O:28])[CH:20]=[CH:21][C:22]4[S:23][CH:24]=[C:25]([Br:27])[CH:26]=4)[C@@H:15]([CH3:29])[C:14]3=[O:30])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 996PhenolHCID 517165Ammonium AcetateHCID 53988546HCID 53988546, compound

Product 1

HCID 53818946(S)-1-(4-Aminoquinolin-7-ylmethyl)-4-[3-(4-bromothiophen-2-yl)acryloyl]-3-methyl-piperazin-2-oneYield 62.2%

Conditions

Temperature
120 °C

Procedure

(S)-1-(4-Chloroquinolin-7-ylmethyl)-4-[3-(4-bromothiophen-2-yl)acryloyl]-3-methyl piperazin-2-one (0.50 g, 0.9 mmol) is treated with phenol (˜2 g) and ammonium acetate (0.5 g, 6.4 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 (gradient elution of 10% of 0.1% aqueous TFA/acetonitrile to 100% acetonitrile) to give the title compound (0.22 g, 0.56 mmol). MS m/z: [M+H]+=485, 487, Cl pattern. 1H NMR (CD3OD, 300 MHz) δ8.2-8.4 (m, 2H), 7.7-7.8 (m, 2H), 7.6 (d, 1H), 7.5 (s, 1H), 7.3 (s, 1H), 6.9-7.0 (m, 1H), 6.7 (d, 1H), 5.0-5.1 (m, 1H), 4.9 (q, 2H), 4.3-4.4 (m, 1H), 3.5-3.7 (m, 2H), 3.3-3.4 (m, 2H), 1.5 (d, 3H).

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 (gradient elution of 10% of 0.1% aqueous TFA/acetonitrile to 100% acetonitrile)

Sources & evidence

ORD record
ord-369968284931482c968598eb739f3c09
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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