Dichloromethane → (S)-4'-(6-Aminopyridin-3-yl)-3'-fluoro-N-(1-hydroxypropan-2-yl)-[1,1'-biphenyl]-2-sulfonamide

HRID 1523903Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11](B(O)O)=[CH:10][C:9]=2[F:17])=[CH:4][CH:3]=1.Br[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[S:25]([NH:28][C@@H:29]([CH3:32])[CH2:30][OH:31])(=[O:27])=[O:26].C(Cl)Cl.C([O-])([O-])=O.[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CS(C)=O>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:19]3[C:20]([S:25]([NH:28][C@@H:29]([CH3:32])[CH2:30][OH:31])(=[O:27])=[O:26])=[CH:21][CH:22]=[CH:23][CH:24]=3)=[CH:10][C:9]=2[F:17])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of (4-(6-aminopyridin-3-yl)-3-fluorophenyl)boronic acid (100 mg, 0.43 mmol), (S)-2-bromo-N-(1-hydroxypropan-2-yl)benzenesulfonamide (160 mg, 0.54 mmol), Pd(dppf)Cl2.CH2Cl2 (18 mg, 0.022 mmol), K2CO3 (340 mg, 2.4 mmol), and DMSO (3 mL) was sparged with nitrogen, then the reaction vessel was sealed and heated at 80° Celsius for 16 hours. The mixture was cooled to rt, then filtered, and subjected to HPLC purification to provide the title compound. MS (CI): mass calcd. for C20H20FN3O3S, 401.12; m/z found, 402.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 8.31-7.93 (m, 5H), 7.72-7.57 (m, 3H), 7.42-7.25 (m, 4H), 7.11-7.04 (d, J=9.2, 1H), 3.34-3.25 (s, 1H), 3.18-3.00 (m, 2H), 1.00-0.91 (d, J=6.5, 3H).

Workup

customthe reaction vessel was sealed
temperatureThe mixture was cooled to rt
filtrationfiltered
customsubjected to HPLC purification

Sources & evidence

ORD record: ord-bfb1a4ac2170486dbce5bba17217744b
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09079866B2

Reaction notes

Loading…