Phosphorus oxychloride → 4,8-Dichloro-2-(4-isopropyl-thiazol-2-yl)-7-(2-morpholin-4-yl-ethoxy)-quinoline

HRID 1422533Notes

Reaction equation

[Cl:1][C:2]1[C:3]([O:21][CH2:22][CH2:23][N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]1[S:13][CH:14]=[C:15]([CH:17]([CH3:19])[CH3:18])[N:16]=1)[CH:8]=[C:7]2O.O=P(Cl)(Cl)[Cl:32]>O1CCOCC1>[Cl:32][C:7]1[C:6]2[C:11](=[C:2]([Cl:1])[C:3]([O:21][CH2:22][CH2:23][N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)=[CH:4][CH:5]=2)[N:10]=[C:9]([C:12]2[S:13][CH:14]=[C:15]([CH:17]([CH3:19])[CH3:18])[N:16]=2)[CH:8]=1

Participants

Conditions

Temperature: 85 °C

Procedure

8-Chloro-2-(4-isopropyl-thiazol-2-yl)-7-(2-morpholin-4-yl-ethoxy)-quinolin-4-ol (5.0 g, 11.5 mmol) in dioxane (50 mL) were stirred at room temperature. POCl3 (5.4 g, 34.6 mmol) was added slowly to the reaction mixture. The reaction was heated to 85° C. with stirring for 10 mins. The reaction was cooled to room temperature and was quenched with ice water. The solution was extracted with ethyl acetate (3×100 mL). The combined organics were dried with sodium sulfate, filtered and were concentrated. Compound XX (4.6 g, 90%) was purified by silica gel chromatography.

Workup

temperatureThe reaction was cooled to room temperature
customwas quenched with ice water
extractionThe solution was extracted with ethyl acetate (3×100 mL)
dry with materialThe combined organics were dried with sodium sulfate
filtrationfiltered
concentrationwere concentrated
customCompound XX (4.6 g, 90%) was purified by silica gel chromatography

Sources & evidence

ORD record: ord-57f47c1dc3c647f582bd50dcb33dea1a
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927484B2

Reaction notes

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