Sodium Carbonate → 2-Chloro-5-(4-chlorophenyl)-10-methyl-7H-isoxazolo[5,4-c]pyrido[2,3-e]azepine

HRID 2401405Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[CH:22]=[CH:21][C:20](OC)=[N:19][C:10]=3[C:11]3[C:17]([CH3:18])=[N:16][O:15][C:12]=3[CH2:13][N:14]=2)=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:27])=O.[OH-].[Na+].C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C>[Cl:27][C:20]1[CH:21]=[CH:22][C:9]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[N:14][CH2:13][C:12]3[O:15][N:16]=[C:17]([CH3:18])[C:11]=3[C:10]=2[N:19]=1

Participants

Conditions

Temperature: 140 °C

Procedure

To 5-(4-chlorophenyl)-2-methoxy-10-methyl-7H-isoxazolo[5,4-c]pyrido[2,3-e]azepine (0.050 g, 0.147 mmol) were added phosphoryl chloride (1 mL, 11 mmol) and DMF (0.1 mL) at room temperature. The reaction was heated to 140° C. for 4 h using microwave irradiation before 2M aq. NaOH and 2M aq. Na2CO3 were added to quench the excess of reagent. The desired product was extracted using EtOAc (repeated 4 times). The organic layers were combined, dried over Na2SO4 and concentrated to dryness. A fraction of the residue was purified by reverse phase chromatography to give the title product as a white solid. LC/MS m/z 344 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 7.80 (d, J=8.52 Hz, 1H), 7.49 (d, J=8.31 Hz, 1H), 7.46 (td, J=2.10, 8.70 Hz, 2H), 7.41 (td, J=2.10, 8.70 Hz, 2H), 4.80 (s, 2H), 2.56 (s, 3H).

Workup

additionwere added
customto quench the excess of reagent
extractionThe desired product was extracted
dry with materialdried over Na2SO4
concentrationconcentrated to dryness
customA fraction of the residue was purified by reverse phase chromatography

Sources & evidence

ORD record: ord-224f9ed71a294ffeb166eaf3328f868c
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08796261B2

Reaction notes

Loading…