Diisopropylethylamine → HCID 57801546, Verbindung

HRID 1669849Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1669849
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[N:11]([CH2:22][C:23]3[CH:31]=[CH:30][C:26]([C:27]([OH:29])=O)=[CH:25][CH:24]=3)[N:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.O[N:33]1[C:37]2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC.[C:63]([OH:69])([C:65](F)(F)F)=[O:64].C(Cl)Cl>C(Cl)Cl.CN(C=O)C.C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:13]=[C:12]([C:14]3[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=3)[N:11]([CH2:22][C:23]3[CH:24]=[CH:25][C:26]([C:27]([NH:33][CH2:37][CH2:65][C:63]([OH:69])=[O:64])=[O:29])=[CH:30][CH:31]=3)[N:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1

Komponenten

8

Edukt 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21863450Trifluoroacetic acid methylene chlorideHCID 67335518HCID 67335518, Verbindung

Produkt 1

HCID 57801546HCID 57801546, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 22350042dichloromethane N,N-dimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of the intermediate from example 73 step D (100 mg, 0.22 mmol) in 1:1 DMF/DCM (0.54 mL) was added 1-hydroxy-7-azabenzo-triazole (35 mg, 0.264 mmol), N,N-diisopropylethyl amine (92 μL, 0.53 mmol) β-alanine-t-butyl ester hydrochloride (48 mg, 0.26 mmol) and 1-(3-(Dimethylamino)propyl-3-ethyl carbodiimide hydrochloride (51 mg, 0.26 mmol). The reaction was left stirring at room temperature for 18 hours. The reaction was diluted with DCM, washed with 1N HCl, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography using 2:5 ethyl acetate-hexanes to give a colorless oil. LC-MS: 4.5 min; (M+H)=580.2. This material was dissolved in 1:1 TFA/DCM (4 mL) and stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo and azeotroped with toluene (1×). The residue was purified by reverse phase HPLC (Gilson) to give the title compound. 1H NMR (DMSO, 500 MHz): δ 8.49 (t, J=5.5 Hz, 1H), 7.88 (d, J=2.1 Hz, 2H), 7.76 (d, J=8.3 Hz, 2H), 7.55 (t, J=1.8 Hz, 1H), 7.39 (d, J=8.7 Hz, 2H), 7.1 (s, 1H), 7.09 (d, J=8.9 Hz, 2H), 7.04 (d, J=9.0 Hz, 2H), 5.47 (s, 2H), 3.79 (s, 3H), 3.45 (q, J=7.1 Hz, 2H), 2.49 (t, J=7.1 Hz, 2H). LC-MS: 3.85 min; (M+H)=524.1.

Aufarbeitung

  1. waitThe reaction was left
  2. washwashed with 1N HCl
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography
  7. customto give a colorless oil
  8. custom4.5 min
  9. stirringstirred at room temperature for 18 hours
  10. concentrationThe reaction mixture was concentrated in vacuo
  11. customazeotroped with toluene (1×)
  12. customThe residue was purified by reverse phase HPLC (Gilson)

Quellen und Nachweise

ORD-Eintrag
ord-df6a93b9f714412386ba303a5fa02840
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US07989475B2

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