Diisopropylethylamine → 2-[3,5-bis(trifluoromethyl)phenyl]-N-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}acetamide

HRID 217524

Reaktionsgleichung

Reaktionsgleichung von HRID 217524
[F:1][C:2]([F:18])([F:17])[C:3]1[CH:4]=[C:5]([CH2:13][C:14](O)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH:52]([C:55]1[CH:56]=[CH:57][C:58]([O:73][CH3:74])=[C:59]([C:61]2[CH:66]=[CH:65][C:64]([C:67]([F:70])([F:69])[F:68])=[CH:63][C:62]=2[CH2:71][NH2:72])[CH:60]=1)([CH3:54])[CH3:53]>C(Cl)Cl.CCOC(C)=O>[F:1][C:2]([F:17])([F:18])[C:3]1[CH:4]=[C:5]([CH2:13][C:14]([NH:72][CH2:71][C:62]2[CH:63]=[C:64]([C:67]([F:68])([F:69])[F:70])[CH:65]=[CH:66][C:61]=2[C:59]2[CH:60]=[C:55]([CH:52]([CH3:54])[CH3:53])[CH:56]=[CH:57][C:58]=2[O:73][CH3:74])=[O:15])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Komponenten

7

Edukt 4

HCID 81531DiisopropylethylamineHCID 1235873,5-Bis(trifluoromethyl)phenylacetic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 591351271-[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine

Produkt 1

HCID 866153972-[3,5-bis(trifluoromethyl)phenyl]-N-{[5'-isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}acetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of 3,5-bis(trifluoromethyl)phenylacetic acid (105.3 mg, 0.387 mmol) in CH2Cl2 (5 mL) was cooled to 0° C. N,N-diisopropylethylamine (169 μL, 0.968 mmol) was added, followed by HATU (139 mg, 0.3667 mmol). The reaction was stirred at 0° C. for 2 minutes and then a solution of 1-[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine (62.5 mg, 0.193 mmol) in CH2Cl2 (2 mL) was added. The reaction was stirred for 1 hour at 0° C. and then diluted with EtOAc (75 mL). The organics were washed with saturated NaHCO3 and brine (25 mL each), dried over Na2SO4, filtered, and concentrated. Purification of the residue by flash chromatography with 100% CH2Cl2 gave 2-[3,5-bis(trifluoromethyl)phenyl]-N-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}acetamide. Rf=0.26 (25% EtOAc/hexanes). LCMS=578.2 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.79 (s, 1H), 7.70 (s, 2H), 7.59 (m, 2H), 7.33 (d, J=8.5 Hz, 1H), 7.25 (m, 1H), 6.97 (d, J=2.0 Hz, 1H), 6.91 (d, J=8.5 Hz, 1H), 5.84 (bs, 1H), 4.48 (dd, J=15.1, 6.6 Hz, 1H), 4.20 (dd, J=14.9, 4.3 Hz, 1H), 3.69 (s, 3H), 3.55 (s, 2H), 2.88 (m, 1H), 1.24 (d, J=6.8 Hz, 6H).

Aufarbeitung

  1. stirringThe reaction was stirred for 1 hour at 0° C.
  2. washThe organics were washed with saturated NaHCO3 and brine (25 mL each)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the residue by flash chromatography with 100% CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-28f3fe5394bb45a0ac3a4a90fd4db27f
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193365B2

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