Triethylamine → 6-Fluoro-5-(5-methoxy-1-benzofuran-2-yl)pyridin-2-amine

HRID 501057Notes

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[CH:17]=[CH:18][C:19]([NH2:23])=[N:20][C:21]=1[F:22].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:21]1[N:20]=[C:19]([NH2:23])[CH:18]=[CH:17][C:16]=1[C:9]1[O:10][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:14][C:7]=2[CH:8]=1

Participants

Conditions

Temperature: 140 °C

Procedure

5-Methoxybenzofuran boronic acid (230 mg, 1.20 mmol), 5-bromo-6-fluoro-pyridin-2-ylamine (191 mg, 1.00 mmol), Pd(PPh3)2Cl2 (16.8 mg, 0.024 mmol) and Et3N (317 μL, 2.27 mmol) were mixed in EtOH (10 mL) in a microwave vial. The reaction mixture was stirred at 140° C. for 15 minutes in a microwave reactor. The volatiles were then removed under reduced pressure, the residue was suspended in water and the product was extracted with ethyl acetate. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. Purification of the crude product by flash column chromatography using 25% ethyl acetate in hexane gave 6-fluoro-5-(5-methoxy-benzofuran-2-yl)-pyridin-2-ylamine (130 mg) as an off-white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ: 8.05-8.21 (m, 1 H) 7.36 (d, J=8.59 Hz, 1 H) 7.03 (d, J=1.95 Hz, 1 H) 6.97 (d, J=3.12 Hz, 1 H) 6.86 (dd, J=8.78, 2.54 Hz, 1 H) 6.45 (d, J=6.63 Hz, 1 H) 4.66 (br. s., 2 H) 3.86 (s, 3 H)

Workup

customThe volatiles were then removed under reduced pressure
extractionthe product was extracted with ethyl acetate
dry with materialThe organic layer was dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification of the crude product by flash column chromatography

Sources & evidence

ORD record: ord-643d79eb21cb448895f98081a367ac5d
Source dataset: uspto-grants-2010_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07772256B2

Reaction notes

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