Anisole → HCID 42597215, compound

HRID 1930246Notes

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-62cb3da758f84e2f990bbd52a05e195a
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188072B2

Reaction notes

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