2,4-Dichloro-5-methoxyaniline → N-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-quinolinyl]acetamide

HRID 396187Notes

Reaction equation

Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([NH:14][C:15](=[O:17])[CH3:16])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:18]#[N:19].[Cl:20][C:21]1[CH:27]=[C:26]([Cl:28])[C:25]([O:29][CH3:30])=[CH:24][C:22]=1[NH2:23].Cl.N1C=CC=CC=1>C(OCCO)C>[C:18]([C:3]1[CH:4]=[N:5][C:6]2[C:11]([C:2]=1[NH:23][C:22]1[CH:24]=[C:25]([O:29][CH3:30])[C:26]([Cl:28])=[CH:27][C:21]=1[Cl:20])=[CH:10][C:9]([O:12][CH3:13])=[C:8]([NH:14][C:15](=[O:17])[CH3:16])[CH:7]=2)#[N:19]

Participants

Conditions

Temperature: 135 °C

Procedure

An amount of 9.7 g (0.035 mol) of N-(4-chloro-3-cyano-6-methoxy-7-quinolinyl)acetamide was stirred in 97 ml of 2-ethoxyethanol. To this were added 2,4-dichloro-5-methoxyaniline (7.4 g, 0.038 mol), and 4.1 g (0.035 mol) pyridine hydrochloride, and the mixture was heated at 135° C. for 3 hours. The solvent was evaporated and the solid was stirred in saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic phase was washed with saturated brine solution, dried over sodium sulfate and evaporated to dryness to give a brown solid (10.7 g, 71% yield), mp 267-270° C.; 1H NMR (DMSO-d6) δ 9.94 (s, 1H), 9.01 (s, 1H), 8.99 (s, 1H), 8.42 (s, 1H), 7.97 (m, 1H), 7.86 (s, 1H), 7.53 (m, 1H), 4.12 (s, 3H), 3.88 (s, 3H), 2.27 (s, 3H); MS (ES) m/z 431.1 (M+1). Analysis for C20H16Cl2N4O3.7H2O: Found: C, 43.23; H, 3.35; N, 10.24. Calcd: C, 43.06; H, 5.38; N, 10.05.

Workup

customThe solvent was evaporated
extractionextracted with ethyl acetate
washThe organic phase was washed with saturated brine solution
dry with materialdried over sodium sulfate
customevaporated to dryness

Sources & evidence

ORD record: ord-97b741e4a85344d68def515d5aa2f45b
Source dataset: uspto-grants-2003_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06608048B2

Reaction notes

Loading…