Hydrochloric Acid → Methyl 4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-3-methylbiphenyl-4-carboxylate

HRID 2356806Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[C:10]([CH3:18])[CH:9]=2)=[CH:4][CH:3]=1.Cl[C:20]1[S:21][C:22]2[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:23]=2[N:24]=1.Cl.O1CCOCC1>C(O)CCC>[F:29][C:27]1[CH:26]=[CH:25][C:23]2[N:24]=[C:20]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([C:8]4[CH:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[C:10]([CH3:18])[CH:9]=4)=[CH:6][CH:7]=3)[S:21][C:22]=2[CH:28]=1

Participants

Conditions

Temperature: 65 °C

Procedure

As shown in Reaction Scheme 7, a mixture of methyl 4′-amino-3-methylbiphenyl-4-carboxylate (0.34 g, 1.40 mmol) and 2-chloro-6-fluoro-1,3-benzothiazole (0.26 g, 1.40 mmol) in n-butanol (4 mL) was heated to 60-70° C., and then 4N HCl in 1,4-dioxane (0.16 mL, 0.63 mmol) was added dropwise with stirring. The reaction mixture was heated at 90° C. for 18 h. Upon cooling to rt, the reaction mixture was concentrated in vacuo. The residue was triturated with ethanol and collected by filtration, yielding 0.32 g (58%) of the title compound as a pale yellow solid. LC/MS m/z 393.3 (MH+), retention time 4.02 min. 1H NMR (400 MHz, CD2Cl2) δ 2.62 (s, 3H), 3.95 (s, 3H), 7.05 (t, 1H), 7.39-7.60 (m, 4H), 7.65 (s, 4H), 7.96 (d, 1H).

Workup

customAs shown in Reaction Scheme 7
temperatureThe reaction mixture was heated at 90° C. for 18 h
temperatureUpon cooling to rt
concentrationthe reaction mixture was concentrated in vacuo
customThe residue was triturated with ethanol
filtrationcollected by filtration

Sources & evidence

ORD record: ord-a2da9a13ee5044a288262dd176f1c88f
Source dataset: uspto-grants-2010_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07759376B2

Reaction notes

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