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 592372노트

반응식

HRID 592372 반응식
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]

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 6228Dimethylformamide용매

반응 조건

온도
120 °C

실험 절차

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]+.

후처리

  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.

출처 및 근거

ORD 기록
ord-e033798b1cdf45a5a0b1687923e5d704
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238644B2

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