Triphenylphosphine → tert-Butyl 4-(5-((4-((2-(1-(methoxycarbonyl)cyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

HRID 592372ノート

反応式

HRID 592372 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:14]=[CH:15][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)=[N:17][CH:18]=2)[N:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:51]([C:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[C:59]1([C:62]([O:64][CH3:65])=[O:63])[CH2:61][CH2:60]1)#[CH:52]>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>[CH3:65][O:64][C:62]([C:59]1([C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=2[C:51]#[C:52][C:2]2[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=[C:4]([NH:12][C:13]3[CH:14]=[CH:15][C:16]([CH:19]4[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]4)=[N:17][CH:18]=3)[N:3]=2)[CH2:61][CH2:60]1)=[O:63]

参加物

7

反応物 3

HCID 11776TriphenylphosphineHCID 86712270Methyl 1-(2-ethynylphenyl)cyclopropanecarboxylateHCID 86712273tert-Butyl 4-(5-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

生成物 1

HCID 86712291tert-Butyl 4-(5-((4-((2-(1-(methoxycarbonyl)cyclopropyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate

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 stirred suspension of tert-butyl 4-(5-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)pyridin-2-yl)piperidine-1-carboxylate (K5) (152 mg, 0.332 mmol), PdCl2(PPh3)2 (12 mg, 0.017 mmol), PPh3 (9 mg, 0.03 mmol), CuI (6 mg, 0.03 mmol) and methyl 1-(2-ethynylphenyl)cyclopropanecarboxylate (K2) (80 mg, 0.40 mmol) in DMF (4.0 mL) was degassed with nitrogen for 10 minutes. Et3N (1.0 mL) was added and the resulting mixture heated under microwave irradiation at 120° C. for 20 minutes. The volatiles were removed in vacuo and the residue was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-60% EtOAc in petroleum benzine 40-60° C. then 10-45% EtOAc in petroleum benzine 40-60° C.) to give the title compound A10 as yellow oil (141 mg, 68%); 1H NMR (400 MHz, d6-DMSO) δ 10.53 (s, 1H), 8.84 (s, 1H), 8.77 (d, J=2.5 Hz, 1H), 8.12 (d, J=6.5 Hz, 1H), 7.61 (dd, J=7.6, 1.0 Hz, 1H), 7.54-7.38 (m, 3H), 7.28 (d, J=8.5 Hz, 1H), 4.05 (br, 2H), 3.51 (s, 3H), 2.94-2.72 (m, 3H), 1.81 (d, J=10.5 Hz, 2H), 1.63 (q, J=4.1 Hz, 2H), 1.61-1.49 (m, 2H), 1.41 (s, 9H), 1.29 (q, J=4.2 Hz, 2H). LCMS-A: rt 5.913 min; m/z 622 [M+H]+.

後処理

  1. customwas degassed with nitrogen for 10 minutes
  2. additionEt3N (1.0 mL) was added
  3. customThe volatiles were removed in vacuo
  4. custompurified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 0-60% EtOAc in petroleum benzine 40-60° C.

出典と根拠

ORDレコード
ord-e033798b1cdf45a5a0b1687923e5d704
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…