Triethylamine → 2-Fluoro-6-(5-methoxy-benzofuran-2-yl)-pyridin-3-ylamine

HRID 501053

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9](B(O)O)=[CH:8][C:7]=2[CH:14]=1.Br[C:16]1[N:21]=[C:20]([F:22])[C:19]([NH2:23])=[CH:18][CH:17]=1.CCN(CC)CC>CCO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:22][C:20]1[C:19]([NH2:23])=[CH:18][CH:17]=[C:16]([C:9]2[O:10][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:14][C:7]=3[CH:8]=2)[N:21]=1

Participants

Conditions

Temperature: 140 °C

Procedure

5-Methoxybenzofuran boronic acid (345 mg, 1.80 mmol), 6-bromo-2-fluoro-pyridin-3-ylamine (286.5 mg, 1.50 mmol), Pd(PPh3)2Cl2 (25.2 mg, 0.036 mmol) and Et3N (475.5 μL, 3.41 mmol) were mixed in EtOH (10 mL) in a microwave vial. The reaction mixture was stirred at 140° C. for 10 minutes in a microwave reactor. The volatiles were then removed under reduced pressure and water was added (20 mL). The product was extracted with ethyl acetate (30 mL). The organic layer was dried over Na2SO4 and concentrated in vacuo. Purification of the crude product by flash column chromatography using 25% ethyl acetate in hexane gave 2-fluoro-6-(5-methoxy-benzofuran-2-yl)-pyridin-3-ylamine (268 mg) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ: 7.58 (d, J=7.6 Hz, 1 H), 7.39 (d, J=9.0 Hz, 1H), 7.15 (m, 1H), 7.14 (s, 1H), 7.04 (d, J=2.6 Hz, 1H), 6.88 (m, 1H), 3.95 (s, 2H), 3.85 (s, 3H). ESMS: m/z 259.47 [M+1]+

Workup

customThe volatiles were then removed under reduced pressure and water
additionwas added (20 mL)
extractionThe product was extracted with ethyl acetate (30 mL)
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated in vacuo
customPurification of the crude product by flash column chromatography

Sources & evidence

ORD record: ord-b61a99674c7c4908a465ba3c7d3591fc
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772256B2

Linked notes

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