Hydrate;hydrochloride → 8-Chloro-2-(4-isopropyl-thiazol-2-yl)-7-(2-morpholin-4-yl-ethoxy)-quinolin-4-ol

HRID 1422532Notes

Reaction equation

[Cl:1][C:2]1[C:3]([O:21][CH2:22][CH:23](OC)OC)=[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]2[OH:20].Cl.[OH2:29]>CC(O)=O>[Cl:1][C:2]1[C:3]([O:21][CH2:22][CH2:23][N:10]2[CH2:11][CH2:2][O:29][CH2:8][CH2:9]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]([CH3:18])[CH3:19])[N:16]=1)[CH:8]=[C:7]2[OH:20]

Participants

Conditions

Temperature: 60 °C

Procedure

8-Chloro-7-(2,2-dimethoxy-ethoxy)-2-(4-isopropyl-thiazol-2-yl)-quinolin-4-ol (5.0 g, 12.3 mmol) was dissolved in HOAc (100 mL) and 1.4 N HCl/H2O (50 mL). The reaction mixture was heated to 60° C. with stirring for 2 hrs. After cooled back to room temperature and concentrated, the residue was co-evaporated with toluene (2×50 mL). Then the crude was dissolved in DCM (100 mL) and cooled to 0° C. with stirring. Morphiline (1.6 g, 18.4 mmol) and NaHB(OAc)3 (3.9 g, 18.4 mmol) were added to the reaction mixture. After stirring at room temperature for 1 h, the reaction mixture was washed with sat. NaHCO3, brine and dried by Na2SO4. After concentration, the crude was purified by silica gel chromatography to afford 5.0 g of 8-chloro-2-(4-isopropyl-thiazol-2-yl)-7-(2-morpholin-4-yl-ethoxy)-quinolin-4-ol as a white solid.

Workup

temperatureAfter cooled back to room temperature
concentrationconcentrated
dissolutionThen the crude was dissolved in DCM (100 mL)
temperaturecooled to 0° C.
stirringwith stirring
stirringAfter stirring at room temperature for 1 h
washthe reaction mixture was washed with sat. NaHCO3, brine
dry with materialdried by Na2SO4
concentrationAfter concentration
customthe crude was purified by silica gel chromatography

Sources & evidence

ORD record: ord-81da5162534242298dab728203f48977
Source dataset: uspto-grants-2015_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08927484B2

Reaction notes

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