Ethyl Acetate → 2-(o-tolyl)-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepine

HRID 1046969Notes

Reaction equation

O=[C:2]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[CH3:26])[CH2:3][N:4]1[C:10](=O)[C:9]2[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=2[NH:7][C:6]2[N:16]=[CH:17][CH:18]=[CH:19][C:5]1=2.C([O-])(=O)C.[NH4+:31].C(OCC)(=O)C.[OH-].[Na+]>C(O)(=O)C>[C:21]1([CH3:26])[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:2]1[N:31]=[C:10]2[C:9]3[CH:12]=[CH:13][CH:14]=[CH:15][C:8]=3[NH:7][C:6]3[N:16]=[CH:17][CH:18]=[CH:19][C:5]=3[N:4]2[CH:3]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a solution of 5-(2-oxo-2-(o-tolyl)ethyl)-5H-benzo[e]pyrido[3,2-b][1,4]diazepin-6(11H)-one (0.6 g, 1 eq.) in acetic acid (10 mL) was added ammonium acetate (2.7 g, 20 eq.). The reaction was stirred at 120° C. for 48 hours. The reaction was poured onto water (50 mL) and ethyl acetate (150 mL). The pH was adjusted to 9 by the addition of NaOH 1N. The phases were separated and washed with water (1×50 mL), brine (1×50 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by column chromatography (10% ethyl acetate in dichloromethane) gave the 2-(o-tolyl)-9H-benzo[f]imidazo[1,2-d]pyrido[2,3-b][1,4]diazepine (0.3 g, 53%). M.p.: 215-217° C.; 1H NMR (DMSO-d6) 400 MHz δ 8.60 (s, 1H), 8.18 (dd, JA=4.4 Hz, JB=1.2 Hz, 1H), 7.99 (dd, JA=8.0 Hz, JB=1.2 Hz, 1H), 7.91-7.85 (m, 2H), 7.82 (s, 1H), 7.34-7.20 (m, 5H), 7.14 (dd, JA=8.0 Hz, JB=4.8 Hz, 1H), 7.05 (t, J=8.4 Hz, 1H), 2.56 (s, 3H); LCMS: 325 [M+H].

Workup

customThe phases were separated
washwashed with water (1×50 mL), brine (1×50 mL)
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customPurification by column chromatography (10% ethyl acetate in dichloromethane)

Sources & evidence

ORD record: ord-254a35d35f014aa7b54af83631ae9b47
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08569331B2

Reaction notes

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