2,4-Dimethoxybenzylamine → 1-(4-{4-Cyano-3-[(2,4-dimethoxybenzyl)amino]isothiazol-5-yl}phenyl)-3-(2-fluoro-5-methylphenyl)urea

HRID 871004Notes

Reaction equation

Cl[C:2]1[C:6]([C:7]#[N:8])=[C:5]([C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][C:19]3[CH:24]=[C:23]([CH3:25])[CH:22]=[CH:21][C:20]=3[F:26])=[O:17])=[CH:11][CH:10]=2)[S:4][N:3]=1.[CH3:27][O:28][C:29]1[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[CH:33][C:30]=1[CH2:31][NH2:32]>C(Cl)Cl>[C:7]([C:6]1[C:2]([NH:32][CH2:31][C:30]2[CH:33]=[CH:34][C:35]([O:37][CH3:38])=[CH:36][C:29]=2[O:28][CH3:27])=[N:3][S:4][C:5]=1[C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([NH:18][C:19]2[CH:24]=[C:23]([CH3:25])[CH:22]=[CH:21][C:20]=2[F:26])=[O:17])=[CH:11][CH:10]=1)#[N:8]

Participants

Conditions

Temperature: 73 °C

Procedure

A suspension of 1-[4-(3-chloro-4-cyanoisothiazol-5-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea (4.3 g, 11.1 mmol) in 15 mL of 2,4-dimethoxybenzylamine was heated to 73° C. for 24 h. The reaction became clear after ˜3 h. The reaction was cooled to RT. The residue was diluted with 300 mL of DCM and was washed with 10% HCl solution two times, saturated Na2S2O5 two times followed by brine. The organic solution was dried with MgSO4, filtered, and concentrated. The crude product was purified by flash silica gel column eluted with 2-5% MTBE in DCM/hexanes (2:1) to obtain the title compound as a light yellow solid (1.19 g, 21%).

Workup

temperatureThe reaction was cooled to RT
washwas washed with 10% HCl solution two times, saturated Na2S2O5 two times
dry with materialThe organic solution was dried with MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude product was purified by flash silica gel column
washeluted with 2-5% MTBE in DCM/hexanes (2:1)

Sources & evidence

ORD record: ord-044bc3cb43a74d2ca08e601ee66cd699
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969583B2

Reaction notes

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