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Triphenylphosphine → tert-Butyl 4-(4-((4-((5-fluoro-2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

HRID 1779013
ノート
印刷プレビュー

反応式

HRID 1779013 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.[C:32]([C:34]1[CH:39]=[C:38]([F:40])[CH:37]=[CH:36][C:35]=1[CH2:41][C:42]([O:44][CH3:45])=[O:43])#[CH:33].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>CN(C=O)C.CCN(CC)CC.CCOC(C)=O.[Cu]I.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>[F:40][C:38]1[CH:37]=[CH:36][C:35]([CH2:41][C:42]([O:44][CH3:45])=[O:43])=[C:34]([C:32]#[C:33][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:18]=[CH:17][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)=[CH:15][CH:14]=3)[N:3]=2)[CH:39]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 3

HCID 11776TriphenylphosphineHCID 86675716Tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylateHCID 86712664Methyl 2-(2-ethynyl-4-fluorophenyl)acetate

生成物 1

HCID 86712665tert-Butyl 4-(4-((4-((5-fluoro-2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

試薬・触媒・溶媒 5

HCID 24350
Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)
触媒
HCID 178418476HCID 178418476、化合物触媒
HCID 6228Dimethylformamide溶媒
HCID 8471Triethylamine溶媒
HCID 8857Ethyl Acetate溶媒

反応条件

温度
120 °C

実験手順

A suspension of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (K5) (0.252 g, 0.552 mmol), methyl 2-(2-ethynyl-4-fluorophenyl)acetate (A50) (0.106 g, 0.552 mmol), PPh3 (0.007 g, 0.03 mmol), CuI (0.005 g, 0.03 mmol) and PdCl2(PPh3)2 (0.019 g, 0.028 mmol) in DMF (3 mL) and Et3N (1.0 mL) was heated under microwave irradiation for 20 minutes at 120° C. The resulting mixture was diluted with EtOAc (100 mL) then washed with water (100 mL), brine (25 mL) and dried over MgSO4. The volatiles were evaporated in vacuo and the residue was adsorbed onto silica gel and purified using column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-80% EtOAc in petroleum benzine 40-60° C.) to give the title compound A51 as a yellow solid (0.158 g, 47%); 1H NMR (400 MHz, CDCl3) δ 8.64 (d, J=1.0 Hz, 1H), 7.75 (s, 1H), 7.62-7.55 (m, 2H), 7.38-7.27 (m, 2H), 7.25-7.19 (m, 2H), 7.14 (td, J=8.3, 2.7 Hz, 1H), 4.36-4.20 (m, 2H), 3.92 (s, 2H), 3.72 (s, 3H), 2.82 (t, J=12.8 Hz, 2H), 2.66 (td, J=8.5, 4.2 Hz, 1H), 1.89-1.78 (m, 2H), 1.70-1.54 (m, 2H), 1.51 (s, 9H). LCMS-A: rt 1.852 min; m/z 613 [M+H]+.

後処理

  1. washthen washed with water (100 mL), brine (25 mL)
  2. dry with materialdried over MgSO4
  3. customThe volatiles were evaporated in vacuo
  4. custompurified
  5. customcolumn chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-80% EtOAc in petroleum benzine 40-60° C.)

出典と根拠

ORDレコード
ord-da374998f973450daff41def4c2fc4e1
出典データセット
uspto-grants-2016_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09266864B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート