1-Hydroxybenzotriazole → 4-[3-(3-Chloro-4-isopropoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-3-methyl-pyridine

HRID 1172918Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14])[C:5]([NH:7][OH:8])=[NH:6].[CH3:16][C:17]1[CH:25]=[N:24][CH:23]=[CH:22][C:18]=1[C:19](O)=O.C1C=CC2N(O)N=NC=2C=1.N=C=N.C(N(C(C)C)CC)(C)C>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[N:6]=[C:19]([C:18]3[CH:22]=[CH:23][N:24]=[CH:25][C:17]=3[CH3:16])[O:8][N:7]=2)[CH:9]=[CH:10][C:11]=1[O:12][CH:13]([CH3:15])[CH3:14]

Participants

Conditions

Temperature: 160 °C

Procedure

To a microwave vial charged with 3-chloro-N-hydroxy-4-isopropoxy-benzamidine (75 mg, 0.328 mmol), 3-methyl-isonicotinic acid (41 mg, 0.298 mmol), HOBt (46 mg, 0.298 mmol), PS-carbodiimide (720 mg, 0.894 mmol, loading 1.24 mmol/g) was added acetonitrile (3.5 mL) and diisopropylethylamine (156 μL, 0.894 mmol). The reaction vial was capped and heated at about 160° C. for about 30 minutes in a Biotage microwave. The reaction mixture was filtered and the resin was washed with acetonitrile (4 mL). Filtrate was concentrated to dryness. The crude product was purified via reverse phase HPLC (30-90% acetonitrile, 30 minute ramp) to give 10.2 mg (10%) of 4-[3-(3-chloro-4-isopropoxy-phenyl)-[1,2,4]oxadiazol-5-yl]-3-methyl-pyridine.

Workup

customThe reaction vial was capped
filtrationThe reaction mixture was filtered
washthe resin was washed with acetonitrile (4 mL)
concentrationFiltrate was concentrated to dryness
customThe crude product was purified via reverse phase HPLC (30-90% acetonitrile, 30 minute ramp)

Sources & evidence

ORD record: ord-4dc39e01fa6242ba936217e2a406435d
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07834039B2

Reaction notes

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