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

HRID 1469860Notes

Reaction equation

HRID 1469860 reaction equation
[F:1][C:2]([F:22])([F:21])[C:3]1[CH:4]=[C:5]([CH:18]=[CH:19][CH:20]=1)[O:6][C:7]1[C:16]2[C:11](=[C:12]([NH2:17])[CH:13]=[CH:14][CH:15]=2)[N:10]=[CH:9][N:8]=1.[F:23][CH:24]([F:41])[C:25]1[N:33]=[CH:32][C:31]([CH2:34][NH:35][C:36](=[O:40])[CH:37]([CH3:39])[CH3:38])=[CH:30][C:26]=1[C:27](O)=[O:28].C(Cl)(=O)C(Cl)=O.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[F:41][CH:24]([F:23])[C:25]1[N:33]=[CH:32][C:31]([CH2:34][NH:35][C:36](=[O:40])[CH:37]([CH3:38])[CH3:39])=[CH:30][C:26]=1[C:27]([NH:17][C:12]1[CH:13]=[CH:14][CH:15]=[C:16]2[C:11]=1[N:10]=[CH:9][N:8]=[C:7]2[O:6][C:5]1[CH:18]=[CH:19][CH:20]=[C:3]([C:2]([F:1])([F:21])[F:22])[CH:4]=1)=[O:28]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 710598402-(Difluoromethyl)-5-(isobutyramidomethyl)nicotinic acidHCID 716803914-(3-(Trifluoromethyl)phenoxy)quinazolin-8-amine

Product 1

HCID 716803932-(Difluoromethyl)-5-(isobutyramidomethyl)-N-(4-(3-(trifluoromethyl)phenoxy)quinazolin-8-yl)nicotinamideYield 9.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

The title compound was prepared following the procedure described in Example-1 using 4-(3-(trifluoromethyl)phenoxy)quinazolin-8-amine (Intermediate-8, 50 mg, 0.18 mmol), 2-(difluoromethyl)-5-(isobutyramidomethyl)nicotinic acid (Intermediate-66, 56 mg, 0.18 mmol), oxalyl chloride (23 mg, 0.18 mmol), DMF (1 drop) and DIPEA (48 mg, 0.37 mmol) in CH2Cl2 (1.5 mL) to afford 10 mg of the title product. 1H NMR (300 MHz, DMSO-d6): δ 10.67 (s, 1H), 8.84-8.82 (d, J=7.8 Hz, 1H), 8.79 (s, 1H), 8.71 (d, J=1.8 Hz, 1H), 8.48 (t, 1H), 8.21-8.19 (d, J=8.4 Hz, 1H), 8.08 (s, 1H), 7.89-7.86 (m, 2H), 7.76 (s, 3H), 7.42-7.06 (t, J=54.6 Hz, 1H), 4.44-4.42 (d, J=5.4 Hz, 2H), 2.44 (m, 1H), 1.05 (d, J=6.6 Hz, 6H); MS [M+H]+: 560.45.

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-a939f4005d5e4f5ba5d86b9e83390b86
Source dataset
uspto-grants-2015_04
Patent number
US09006257B2

Reaction notes

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