Triethylamine → tert-Butyl 4-(4-((4-((2-(1-amino-1-oxobutan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

HRID 592359ノート

反応式

HRID 592359 の反応式
Cl[C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)=[CH:15][CH:14]=2)[N:3]=1.F[B-](F)(F)F.[C:37]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[CH:45]([CH2:49][CH3:50])[C:46]([NH2:48])=[O:47])#[CH:38].CCN(CC)CC>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[NH2:48][C:46](=[O:47])[CH:45]([C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=1[C:37]#[C:38][C:2]1[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([CH:19]3[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]3)=[CH:15][CH:14]=2)[N:3]=1)[CH2:49][CH3:50]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 26255TetrafluoroborateHCID 86675716Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylateHCID 867122692-(2-Ethynylphenyl)butanamide

生成物 1

HCID 86712282tert-Butyl 4-(4-((4-((2-(1-amino-1-oxobutan-2-yl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate収率 68.2%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
120 °C

実験手順

A mixture of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (K3) (193 mg, 0.422 mmol), PdCl2(PPh3)2 (15 mg, 0.021 mmol), t-Bu3PH.BF4 (6 mg, 0.021 mmol), CuI (4 mg, 0.021 mmol) and 2-(2-ethynylphenyl)butanamide (K1) (87 mg, 0.47 mmol) in DMF (3.0 mL) was degassed with nitrogen for 10 minutes. Et3N (1.0 mL) was added and the resulting mixture was heated under microwave irradiation at 120° C. for 20 minutes. The volatiles were removed under reduced pressure and the residue was adsorbed onto silica gel then purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.) to give the title compound A1 as a yellow solid (175 mg, 68%); 1H NMR (400 MHz, d6-DMSO) δ 10.39 (s, 1H), 8.88-8.76 (m, 1H), 7.67 (d, J=8.5 Hz, 2H), 7.63-7.47 (m, 3H), 7.37 (td, J=7.4, 1.6 Hz, 1H), 7.27-7.17 (m, 3H), 7.01 (s, 1H), 4.07 (s, 2H), 3.89 (dd, J=8.6, 6.4 Hz, 1H), 2.80 (br, 2H), 2.64 (J m, 1H), 1.98-1.90 (m, 1H), 1.74 (d, J=12.7 Hz, 2H), 1.70-1.60 (m, 1H), 1.55-1.44 (m, 2H), 1.42 (s, 9H), 0.87 (t, J=7.3 Hz, 3H). LCMS-A: rt 6.726 min; m/z 606 [M−H]−.

後処理

  1. customThe volatiles were removed under reduced pressure
  2. customthen purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.)

出典と根拠

ORDレコード
ord-3e2efca6b1644a8b86c5c372d46224bc
出典データセット
uspto-grants-2016_01
特許番号
US09238644B2

反応ノート

読み込み中…