4-Chlorobenzylamine → 1-(4-chlorobenzyl)-3-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-8-yl)urea

HRID 1505198Notes

Reaction equation

[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl.[N-:22]=[C:23]=[O:24].N[C:26]1[C:31]2[O:32][CH2:33][C:34](=[O:36])[NH:35][C:30]=2[CH:29]=[CH:28][CH:27]=1>CCOC(C)=O.CN(C=O)C>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH:7][C:23]([NH:22][C:26]2[C:31]3[O:32][CH2:33][C:34](=[O:36])[NH:35][C:30]=3[CH:29]=[CH:28][CH:27]=2)=[O:24])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Commercially available p-chlorobenzylamine (0.98 ml, 8 mmol) was dissolved in 40 ml of AcOEt and at 0° C. triphosgene (2.37 g, 1 equiv.) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and the residue was dissolved in 20 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1f (1.42 g, 7.11 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt 1/petroleum ether 1). The solvent was evaporated and to the crude 5% HCl was added. The solid was filtrated, washed with water, MeOH and diethyl ether obtaining 1.6 g of a white product. Yield=68% 1HNMR (DMSO, 200 MHz) δ 4.27 (2H, d, J=5.6 Hz), 4.61 (2H, s), 6.47 (1H, dd, J=7.8 Hz, J′=1.2 Hz), 6.81 (1H, t, J=8.2 Hz), 7.35 (5H, m), 7.73 (1H, dd, J=8.2 Hz, J′=1.2 Hz), 8.10 (1H, bs), 10.65 (1H, bs); [M+1] 332.4 (C16H14ClN3O3 requires 331.75).

Workup

additionwas added to the solution
customthen evaporated
dissolutionthe residue was dissolved in 20 ml of DMF
temperaturethe mixture was warmed at 80° C. for 8 hours
customThe solvent was evaporated
additionto the crude 5% HCl was added
filtrationThe solid was filtrated
washwashed with water, MeOH and diethyl ether obtaining 1.6 g of a white product

Sources & evidence

ORD record: ord-36e135a1b71642afab4b6a26485718d6
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216975B2

Reaction notes

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