Anisole → HCID 42597215, compound

HRID 1256206Notes

Reaction equation

[Cl:1][C:2]1[CH:37]=[CH:36][C:5]2[N:6](CC3C=CC(OC)=CC=3)[C:7](=[O:26])[CH:8]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH3:25])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.C1(OC)C=CC=CC=1.[Al+3].[Cl-].[Cl-].[Cl-]>ClC(Cl)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:37]=[CH:36][C:5]2[NH:6][C:7](=[O:26])[CH:8]([CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH3:25])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 85 °C

Procedure

7-Chloro-5-(4-fluorophenyl)-1-(4-methoxybenzyl)-3-(2-methylbenzyl)-1H-benzo[e][1,4]diazepin-2(3H)-one (44 mg, 0.086 mmol) was dissolved in dichloroethane (1 mL) under nitrogen and 200 μL of anisole was added followed by AlCl3 (69 mg, 0.515 mmol). This mixture was heated to 85° C. for 2.5 h then allowed to cool and diluted with ethyl acetate and ice. This biphasic mixture was stirred vigorously for 20 min, then partitioned, and the organic layer was washed with water twice, then brine once. The aqueous layers were back-extracted once with ethyl acetate, and the combined organic extracts dried over MgSO4. Chromatography on silica gel (5%-30%-40%-50% ethyl acetate in hexanes) provided the title compound (27 mg, 80%) as a yellow solid. APCI MS m/z 415.1 [M+Na+], 393.1 [M+H+]; 1H NMR (300 MHz, CDCl3) δ 9.28 (s, 1H), 7.61-7.16 (m, 11H), 3.91 (t, J=7 Hz, 1H), 3.72-3.69 (m, 2H), 2.50 (s, 3H).

Workup

temperatureto cool
custompartitioned
washthe organic layer was washed with water twice
extractionThe aqueous layers were back-extracted once with ethyl acetate
dry with materialthe combined organic extracts dried over MgSO4

Sources & evidence

ORD record: ord-3fc631e2d31147148979d7af32e7885d
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08461153B2

Reaction notes

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