Phosphorus oxychloride → 2-chloro-7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinoline

HRID 81983Notes

Reaction equation

[CH3:1][C:2]1[C:6]([C:7]2[C:8]([O:28][CH3:29])=[CH:9][C:10]3[C:11]4[N:19]([CH2:20][CH:21]5[CH2:26][CH2:25][O:24][CH2:23][CH2:22]5)[C:18](=O)[NH:17][C:12]=4[CH:13]=[N:14][C:15]=3[CH:16]=2)=[C:5]([CH3:30])[O:4][N:3]=1.O=P(Cl)(Cl)[Cl:33].P(Cl)(Cl)(Cl)(Cl)Cl>C(Cl)Cl>[Cl:33][C:18]1[N:19]([CH2:20][CH:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[C:11]2[C:10]3[CH:9]=[C:8]([O:28][CH3:29])[C:7]([C:6]4[C:2]([CH3:1])=[N:3][O:4][C:5]=4[CH3:30])=[CH:16][C:15]=3[N:14]=[CH:13][C:12]=2[N:17]=1

Participants

Conditions

Temperature: 120 °C

Procedure

7-(3,5-Dimethyl-4-isoxazolyl)-8-(methyloxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one (for a preparation see Intermediate 14) (220 mg, 0.539 mmol) was dissolved in POCl3 (2 ml, 21.46 mmol), PCl5 (0.2 g, 0.960 mmol) was added and the mixture was heated at 120° C. for 24 h. The reaction mixture was evaporated in vacuo to give a beige solid. This was dissolved in DCM (3 ml) and loaded onto a 25 g silica column, then eluted with 0-10% 2M methanolic ammonia/DCM (25 column volumes) and product containing fractions were evaporated in vacuo to give 2-chloro-7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinoline (14.2 mg, 0.033 mmol, 6.18% yield) as beige solid. LCMS (formate) Rt 0.81 min, MH+ 427.

Workup

customThe reaction mixture was evaporated in vacuo
customto give a beige solid
washeluted with 0-10% 2M methanolic ammonia/DCM (25 column volumes) and product
additioncontaining fractions
customwere evaporated in vacuo

Sources & evidence

ORD record: ord-1f45e2df9a42415691a23b10224fcca5
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846709B2

Reaction notes

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