Triethylamine → Methyl 2-(2-((2-(4-(1-(tert-butoxycarbonylamino)ethyl)phenylamino)-5-(trifluoromethyl)pyrimidin-4-yl)ethynyl)phenyl)acetate

HRID 1779028Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1779028
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]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH3:20])=[CH:15][CH:14]=2)[N:3]=1.CCN(CC)CC.[C:36]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=1[CH2:44][C:45]([O:47][CH3:48])=[O:46])#[CH:37].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>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>[C:24]([O:23][C:22]([NH:21][CH:19]([C:16]1[CH:17]=[CH:18][C:13]([NH:12][C:4]2[N:3]=[C:2]([C:37]#[C:36][C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=3[CH2:44][C:45]([O:47][CH3:48])=[O:46])[C:7]([C:8]([F:11])([F:10])[F:9])=[CH:6][N:5]=2)=[CH:14][CH:15]=1)[CH3:20])=[O:28])([CH3:27])([CH3:26])[CH3:25]

Komponenten

8

Edukt 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 45789861Methyl 2-(2-ethynylphenyl)acetateHCID 76611269Tert-butyl 1-(4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate

Produkt 1

HCID 86712677Methyl 2-(2-((2-(4-(1-(tert-butoxycarbonylamino)ethyl)phenylamino)-5-(trifluoromethyl)pyrimidin-4-yl)ethynyl)phenyl)acetate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A suspension of tert-butyl 1-(4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)phenyl)ethylcarbamate (A63) (487 mg, 1.17 mmol), Et3N (760 μL), methyl 2-(2-ethynylphenyl)acetate (K1) (244 mg, 1.40 mmol), PdCl2(PPh3)2 (41 mg, 0.058 mmol), CuI (22.0 mg, 0.117 mmol) and PPh3 (36.0 mg, 0.117 mmol) in DMF (4.6 mL) was heated under microwave irradiation at 120° C. for 15 minutes. The volatiles were evaporated in vacuo and the residue purified by silica gel column chromatography (CombiFlash Rf, SiO2 cartridge, 0-25% EtOAc in cyclohexane) to give the title compound A64 as a yellow solid (400 mg, 62%); 1H NMR (300 MHz, CDCl3) δ 8.66 (s, 1H), 7.70 (dd, J=7.83, 1.17 Hz, 1H), 7.61 (d, J=8.61 Hz, 2H), 7.43 (m, 3H), 7.34 (d, J=8.40 Hz, 2H), 4.78 (m, 2H), 3.98 (s, 2H), 3.73 (s, 3H), 1.61 (s, 1H, peak obscured), 1.46 (m, 12H). LCMS-B: rt 8.90 min; m/z 555 [M+H]+.

Aufarbeitung

  1. customThe volatiles were evaporated in vacuo
  2. customthe residue purified by silica gel column chromatography (CombiFlash Rf, SiO2 cartridge, 0-25% EtOAc in cyclohexane)

Quellen und Nachweise

ORD-Eintrag
ord-2d9599048d5f4f388a660f7e2b7bca50
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09266864B2

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