Lawesson's reagent → 2-((S)-1-(8-chloro-2-(5-methyl-1,3,4-thiadiazol-2-yl)quinolin-3-yl)ethyl)isoindoline-1,3-dione

HRID 216822Notes

Reaction equation

[C:1]([NH:4][NH:5][C:6]([C:8]1[C:17]([C@@H:18]([N:20]2[C:28](=[O:29])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]2=[O:30])[CH3:19])=[CH:16][C:15]2[C:10](=[C:11]([Cl:31])[CH:12]=[CH:13][CH:14]=2)[N:9]=1)=O)(=O)[CH3:2].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:41])=CC=1>C1COCC1.C1(C)C=CC=CC=1>[Cl:31][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:10]=1[N:9]=[C:8]([C:6]1[S:41][C:1]([CH3:2])=[N:4][N:5]=1)[C:17]([C@@H:18]([N:20]1[C:28](=[O:29])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21]1=[O:30])[CH3:19])=[CH:16]2

Participants

Conditions

Temperature: 120 °C

Procedure

To a stirred solution of (S)—N′-acetyl-8-chloro-3-(1-(1,3-dioxoisoindolin-2-yl)-ethyl)quinoline-2-carbohydrazide (85 mg, 0.19 mmol) in THF (1.5 mL) and toluene (3.0 mL) was added Lawesson's reagent (118 mg, 0.29 mmol). The reaction was heated in the microwave at 120° C. for 20 minutes and then cooled to room temperature and purified by column chromatography (SiO2, 12 g, hexanes:ethyl acetate, 1:0 to 1:1) to give 2-((S)-1-(8-chloro-2-(5-methyl-1,3,4-thiadiazol-2-yl)quinolin-3-yl)ethyl)isoindoline-1,3-dione. 1H NMR (400 MHz, CDCl3) δ ppm 8.63 (1H, s), 7.77-7.84 (4H, m), 7.70 (2H, dd, J=5.3, 2.9 Hz), 7.46-7.51 (1H, m), 7.06 (1H, q, J=7.0 Hz), 2.85 (3H, s), 2.11 (3H, d, J=7.0 Hz).

Workup

temperaturecooled to room temperature
custompurified by column chromatography (SiO2, 12 g, hexanes:ethyl acetate, 1:0 to 1:1)

Sources & evidence

ORD record: ord-252fcacaf59142738bad304228cb0c76
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193199B2

Reaction notes

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