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

HRID 1469860ノート

反応式

HRID 1469860 の反応式
[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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  1. customThe title compound was prepared

出典と根拠

ORDレコード
ord-a939f4005d5e4f5ba5d86b9e83390b86
出典データセット
uspto-grants-2015_04
特許番号
US09006257B2

反応ノート

読み込み中…