Benzenesulfonic Acid → 3-(3-Chloro-4-fluorophenyl)thieno[3,2-c]pyridin-4-amine

HRID 734311Notes

Reaction equation

[NH2:1][C:2]1[C:7]2[C:8](Br)=[CH:9][S:10][C:6]=2[CH:5]=[CH:4][N:3]=1.[Cl:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][C:18]=1[F:19].C(=O)([O-])[O-].[Na+].[Na+].C1(S(O)(=O)=O)C=CC=CC=1>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[C:7]2[C:8]([C:15]3[CH:16]=[CH:17][C:18]([F:19])=[C:13]([Cl:12])[CH:14]=3)=[CH:9][S:10][C:6]=2[CH:5]=[CH:4][N:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

The mixture of 4-amino-3-bromo-thieno[3,2-c]pyridine (12) (300 mg 1.24 mmol), 3-chloro-4-fluoro-benzenboronic acid (432 mg, 2.48 mmol), Pd(PPh3)4 (215 mg, 10 mol %) and sodium carbonate (3.1 ml, 6.0 mmol) in 30 ml of DME was stirred for 14 hours at 80° C. The resultant mixture was directly applied to SCX (benzenesulphonicacid-based strong cation exchange sorbent:Varian, 10 g) and eluted with 1N NH3 in CHCl3 and MeOH. The eluant was collected and concentrated in vacuo. The residue was purified by chromatography on a silica gel column to afford the title compound (295 mg). 1H NMR (400 MHz, DMSO-d6) ppm 7.58 (d, J=5.6 Hz, 1H), 7.71 (dd, J=2.1, 7.2 Hz, 1H), 7.57 (s, 1H), 7.54 (dd, J=9.1 Hz, 1H), 7.47 (ddd, J=2.1, 4.8, 8.5 Hz, 1H), 7.29 (d. J=5.8 Hz, 1H), 5.42 (s, 2H). MS: m/z 279, 281 (M+H)+.

Workup

washeluted with 1N NH3 in CHCl3 and MeOH
customThe eluant was collected
concentrationconcentrated in vacuo
customThe residue was purified by chromatography on a silica gel column

Sources & evidence

ORD record: ord-12aedd826f5047cb88879bc726e589fa
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07592352B2

Reaction notes

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