2,3-Dichlorobenzoic acid → 2,3-Dichloro-N-[[4,4-difluoro-1-(6-fluoro-3-pyridyl)cyclohexyl]methyl]benzamide

HRID 512226Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 512226
[F:1][C:2]1([F:17])[CH2:7][CH2:6][C:5]([CH2:15][NH2:16])([C:8]2[CH:9]=[N:10][C:11]([F:14])=[CH:12][CH:13]=2)[CH2:4][CH2:3]1.[Cl:18][C:19]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:20]=1[C:21](O)=[O:22].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C>CN(C=O)C.O>[Cl:18][C:19]1[C:27]([Cl:28])=[CH:26][CH:25]=[CH:24][C:20]=1[C:21]([NH:16][CH2:15][C:5]1([C:8]2[CH:9]=[N:10][C:11]([F:14])=[CH:12][CH:13]=2)[CH2:4][CH2:3][C:2]([F:1])([F:17])[CH2:7][CH2:6]1)=[O:22]

Komponenten

8

Edukt 5

HCID 57652,3-Dichlorobenzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86716261[4,4-Difluoro-1-(6-fluoro-pyridin-3-yl)-cyclohexyl]-methylamine

Produkt 1

HCID 867162602,3-Dichloro-N-[[4,4-difluoro-1-(6-fluoro-3-pyridyl)cyclohexyl]methyl]benzamideAusbeute 38,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of C-[4,4-difluoro-1-(6-fluoro-pyridin-3-yl)-cyclohexyl]-methylamine (38 mg, 0.157 mmol), 2,3-dichlorobenzoic acid (30 mg, 0.157 mmol), HOBt (25 mg, 0.185 mmol), EDCI.HCl (36 mg, 0.185 mmol) and DIPEA (48 mg, 0.345 mmol) in DMF (2 mL) was stirred at room temperature overnight. Water was added to the solution followed by extraction with EtOAc (3×10 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by Prep. HPLC to give the title compound (25 mg, yield: 38%). 1H NMR (CDCl3 300 MHz): δ ppm 8.18 (d, J=2.8 Hz, 1H), 7.89-7.80 (m, 1H), 7.50 (dd, J=8.0 Hz, 2.0 Hz, 1H), 7.33 (dd, J=7.6 Hz, 1.6 Hz, 1H), 7.28-7.18 (m, 1H), 6.98 (dd, J=8.8 Hz, 3.2 Hz, 1H), 5.85 (t, J=6.8 Hz, 1H), 3.64 (d, J=6.8 Hz, 2H), 2.36-2.00 (m, 6H), 1.87-1.65 (m, 2H). LCMS (MH+): m/z=417.1, tR (minutes, Method C)=1.11

Aufarbeitung

  1. extractionfollowed by extraction with EtOAc (3×10 ml)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product was purified by Prep

Quellen und Nachweise

ORD-Eintrag
ord-0f306096c9854ebaaa1c391b1fdd9c55
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09102591B2

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