Phenol → 1-(4-Aminocinnolin-7-ylmethyl)-4-[2-(5-chlorothiophen-2-yl)-ethenesulfonyl]-piperazin-2-one

HRID 1432996Notes

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]([S:19]([CH:22]=[CH:23][C:24]4[S:25][C:26]([Cl:29])=[CH:27][CH:28]=4)(=[O:21])=[O:20])[CH2:15][C:14]3=[O:30])=[CH:9][CH:10]=2)[N:5]=[N:4][CH:3]=1.C1(O)C=CC=CC=1.C([O-])(=O)C.[NH4+:42]>C(OCC)(=O)C>[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]([S:19]([CH:22]=[CH:23][C:24]4[S:25][C:26]([Cl:29])=[CH:27][CH:28]=4)(=[O:20])=[O:21])[CH2:15][C:14]3=[O:30])=[CH:9][CH:10]=2)[N:5]=[N:4][CH:3]=1

Participants

Conditions

Temperature: 120 °C

Procedure

1-(4-Chlorocinnolin-7-ylmethyl)-4-[2-(5-chlorothiophen-2-yl)-ethenesulfonyl]-piperazin-2-one (0.06 g, 0.12 mmol) is treated with phenol (0.20 g) and ammonium acetate (0.2 g, 2.6 mmol) and heated to 120° C. for 45 minutes. The reaction mixture is cooled, diluted with ethyl acetate and washed with 1 N NaOH (3×100 mL) and water. The organic layer is concentrated and the residue is purified by reverse phase HPLC (20% aqueous TFA (0.1%)/acetonitrile to 100% acetonitrile). Fractions containing the desired product are lyophilized to obtain the title compound (0.02 g, 0.043 mmol). MS m/z: [M+H]+=464; 1H NMR (CD3OD, 300 MHz) δ8.6 (s, 1H), 8.4 (d, 1H), 7.75 (d, 1H), 7.65 (d, 1H), 7.35 (d, 1H), 7.1 (d, 1H), 6.8 (d, 1H), 4.9 (s, 2H), 4.05 (s, 2H), 3.6 (m, 4H).

Workup

temperatureThe reaction mixture is cooled
washwashed with 1 N NaOH (3×100 mL) and water
concentrationThe organic layer is concentrated
customthe residue is purified by reverse phase HPLC (20% aqueous TFA (0.1%)/acetonitrile to 100% acetonitrile)
additionFractions containing the desired product

Sources & evidence

ORD record: ord-2aca009ef11c496cbbacc5ae4fd799a7
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07612075B2

Reaction notes

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