Water → N-(6-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzothiazol-2-yl)-acetamide

HRID 216262Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([C:10]2[CH:22]=[CH:21][C:13]3[N:14]=[C:15]([NH:17][C:18](=[O:20])[CH3:19])[S:16][C:12]=3[CH:11]=2)[CH:3]=1.[Cl:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1[CH2:31][CH2:32][NH2:33].C([O-])([O-])=O.[K+].[K+].O>CN1CCCC1=O>[Cl:23][C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[CH:26][C:25]=1[CH2:31][CH2:32][NH:33][C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([C:10]2[CH:22]=[CH:21][C:13]3[N:14]=[C:15]([NH:17][C:18](=[O:20])[CH3:19])[S:16][C:12]=3[CH:11]=2)[CH:3]=1

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of N-[6-(6-chloro-2-methoxy-pyrimidin-4-yl)-benzothiazol-2-yl]-acetamide (160 mg, 0.48 mmol), 2-(2,4-dichloro-phenyl)-ethylamine (362 μL, 2.4 mmol), and K2CO3 (359 mg, 2.6 mmol) in N-methylpyrrolidinone (2.6 mL) is heated to 140° C. Water (20 mL) is added after 1 hour of heating and extracted with EtOAc (20 mL). The organic extracts are combined and dried over magnesium sulfate, filtered and evaporated. This residue is subjected to chromatography on silica gel eluting with 90% ethyl acetate:heptane to afford a solid which is triturated with 1:1 methanol:ethyl acetate. The solid is collected to afford N-(6-{6-[2-(2,4-dichloro-phenyl)-ethylamino]-2-methoxy-pyrimidin-4-yl}-benzothiazol-2-yl)-acetamide [31 mg, 13%, Example 94]. LCMS RT=2.49 minutes, MS: 488 (M+H). IC50=11 nM

Workup

temperatureof heating
extractionextracted with EtOAc (20 mL)
dry with materialdried over magnesium sulfate
filtrationfiltered
customevaporated
customheptane to afford a solid which
customis triturated with 1:1 methanol
customThe solid is collected

Sources & evidence

ORD record: ord-dea17b0d9bb9450d830eda46377fd5bf
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193183B2

Reaction notes

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