N-bromobutanimide → 2-Amino-4-(2,4-dichlorophenyl)thiazole-5-carbonitrile

HRID 2282297Notes

Reaction equation

C(O)[C@H]1O[C@@H]2O[C@H]3[C@H](O)[C@@H](O)[C@@H](O[C@H]4[C@H](O)[C@@H](O)[C@@H](O[C@H]5[C@H](O)[C@@H](O)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@@H](O[C@H]7[C@H](O)[C@@H](O)[C@@H](O[C@H]8[C@H](O)[C@@H](O)[C@@H](O[C@H]1[C@H](O)[C@H]2O)O[C@@H]8CO)O[C@@H]7CO)O[C@@H]6CO)O[C@@H]5CO)O[C@@H]4CO)O[C@@H]3CO.[Cl:78][C:79]1[CH:84]=[C:83]([Cl:85])[CH:82]=[CH:81][C:80]=1[C:86](=O)[CH2:87][C:88]#[N:89].C1C(=O)N(Br)C(=O)C1.[NH2:99][C:100]([NH2:102])=[S:101]>O.CC(C)=O>[NH2:102][C:100]1[S:101][C:87]([C:88]#[N:89])=[C:86]([C:80]2[CH:81]=[CH:82][C:83]([Cl:85])=[CH:84][C:79]=2[Cl:78])[N:99]=1

Participants

Conditions

Temperature: 50 °C

Procedure

beta-Cyclodextrin (4.29 g, 3.78 mmol) was dissolved in water (75 mL) at 50° C. and a solution of 3-(2,4-dichlorophenyl)-3-oxopropanenitrile (810 mg, 3.8 mmol) in Acetone (3.80 mL) was added dropwise, followed by NBS (0.808 g, 4.54 mmol) and thiourea (0.346 g, 4.54 mmol). Reaction mixture was stirred at 50° C. 1 hr. LCMS indicated complete conversion. Reaction mixture was cooled to rt, extracted with ethyl acetate (3×50 mL), dried with MgSO4, filtered and concentrated under reduced pressure. The residue was purified by ISCO with 5-30% ethyl acetate in hexanes to give 0.43 g of the title compound (42%). LCMS: (FA) ES+, 270, 272. 1H NMR (400 MHz, d1-chloroform) δ 7.49 (d, J=1.84 Hz, 1H), 7.41 (d, J=8.30 Hz, 1H), 7.31 (dd, J=8.16, 1.74 Hz, 1H).

Workup

customReaction mixture
custom1 hr
customReaction mixture
temperaturewas cooled to rt
extractionextracted with ethyl acetate (3×50 mL)
dry with materialdried with MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by ISCO with 5-30% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-bedf96aa40ba47c5934efe4577cb190b
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139589B2

Reaction notes

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