Oxalyl chloride → 2-(Difluoromethyl)-N-(4-(4-fluoro-3-(trifluoromethyl)phenoxy)quinolin-8-yl)-5-(isobutyramidomethyl)nicotinamide

HRID 1469866Notes

Reaction equation

HRID 1469866 reaction equation
[F:1][C:2]1[CH:19]=[CH:18][C:5]([O:6][C:7]2[C:16]3[C:11](=[C:12]([NH2:17])[CH:13]=[CH:14][CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][C:3]=1[C:20]([F:23])([F:22])[F:21].[F:24][CH:25]([F:42])[C:26]1[N:34]=[CH:33][C:32]([CH2:35][NH:36][C:37](=[O:41])[CH:38]([CH3:40])[CH3:39])=[CH:31][C:27]=1[C:28](O)=[O:29].C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[F:42][CH:25]([F:24])[C:26]1[N:34]=[CH:33][C:32]([CH2:35][NH:36][C:37](=[O:41])[CH:38]([CH3:39])[CH3:40])=[CH:31][C:27]=1[C:28]([NH:17][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:11]=1[N:10]=[CH:9][CH:8]=[C:7]2[O:6][C:5]1[CH:18]=[CH:19][C:2]([F:1])=[C:3]([C:20]([F:23])([F:21])[F:22])[CH:4]=1)=[O:29]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 710598402-(Difluoromethyl)-5-(isobutyramidomethyl)nicotinic acidHCID 716780484-(4-Fluoro-3-(trifluoromethyl)phenoxy)quinolin-8-amine

Product 1

HCID 716803902-(Difluoromethyl)-N-(4-(4-fluoro-3-(trifluoromethyl)phenoxy)quinolin-8-yl)-5-(isobutyramidomethyl)nicotinamideYield 7.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared following the procedure described in Example-1 using 4-(4-fluoro-3-(trifluoromethyl)phenoxy)quinolin-8-amine (Intermediate-44, 50 mg, 0.16 mmol), 2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinic acid (Intermediate-66, 52 mg, 0.19 mmol), oxalyl chloride (37 mg, 0.29 mmol), DMF (1 drop) and DIPEA (74 mg, 0.57 mmol) in CH2Cl2 (2 mL) to afford 7 mg of the title product. 1H NMR (300 MHz, CDCl3): δ 10.39 (s, 1H), 8.93 (d, 1H), 8.75 (s, 1H), 8.60 (d, 1H), 8.07 (m, 2H), 7.66 (t, 1H), 7.47 (m, 1H), 7.37-7.15 (m, 2H), 6.60 (d, J=5.4 Hz, 1H), 4.63-4.60 (d, J=6.9 Hz, 2H), 2.45 (m, 1H), 1.21 (d, J=6.9 Hz, 6H); MS (m/z): 577.97 (M+H)+.

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-2299984f914e4a50aaf6062bebbafee9
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

Loading…