Acetic Acid → HCID 71014126, Verbindung

HRID 1430080Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1430080
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([C:12]([NH:14][C@H:15]1[CH2:20][CH2:19][CH2:18][CH2:17][C@@H:16]1[OH:21])=[O:13])[CH:8]=[C:7]2[CH:22]=O.Cl.Cl.[Cl:26][C:27]1[CH:32]=[CH:31][N:30]=[C:29]([C:33]2([F:39])[CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[CH:28]=1.C(O)(=O)C.C([BH3-])#N>ClCCCl.C(N(CC)CC)C.C(Cl)Cl>[Cl:26][C:27]1[CH:32]=[CH:31][N:30]=[C:29]([C:33]2([F:39])[CH2:34][CH2:35][N:36]([CH2:22][C:7]3[C:6]4[C:11](=[C:2]([F:1])[CH:3]=[CH:4][CH:5]=4)[N:10]=[C:9]([C:12]([NH:14][C@H:15]4[CH2:20][CH2:19][CH2:18][CH2:17][C@@H:16]4[OH:21])=[O:13])[CH:8]=3)[CH2:37][CH2:38]2)[CH:28]=1

Komponenten

8

Edukt 4

HCID 176Acetic AcidHCID 498716Cyano-borohydrideHCID 86726469HCID 86726469, VerbindungHCID 86726471HCID 86726471, Verbindung

Produkt 1

HCID 71014126HCID 71014126, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 8471TriethylamineKatalysatorHCID 111,2-DichloroethaneLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 8-fluoro-4-formyl-N-[(1S,2S)-2-hydroxycyclohexyl]quinoline-2-carboxamide (C9) (0.080 g, 0.25 mmol) in DCE (3 mL) was 4-chloro-2-(4-fluoropiperidin-4-yl)pyridine dihydrochloride (C5) (0.080 g, 0.28 mmol) and triethylamine (6 drops). After 5 min, acetic acid (0.043 mL, 0.76 mmol) and MP-cyanoborohydride were added. The mixture was irradiated in a microwave reactor at 100° C. for 20 min, then diluted with CH2Cl2 and was washed with brine. The organic solution was dried over sodium sulfate, filtered, and concentrated in vacuo. The resultant residue was purified via silica gel chromatography eluting with 0-5% methanol in dichloromethane to provide the title compound (Example C) as a white solid that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 515.0 for M+H+. 1H NMR (400 MHz, CDCl3) δ 8.44 (d, J=5.2 Hz, 1H), 8.38 (s, 1H), 8.29 (d, J=7.8 Hz, 1H), 8.17 (d, J=8.5 Hz, 1H), 7.60-7.55 (m, 2H), 7.47-7.42 (m, 1H), 7.22-7.20 (m, 1H), 4.03 (s, 2H), 3.94-3.86 (m, 1H), 3.63-3.56 (m, 1H), 3.42 (br s, 1H), 2.86-2.83 (m, 2H), 2.62-2.56 (m, 2H), 2.47-2.30 (m, 2H), 2.17-2.11 (m, 2H), 1.89-1.78 (m, 4H), 1.56-1.31 (m, 4H).

Aufarbeitung

  1. customThe mixture was irradiated in a microwave reactor at 100° C. for 20 min
  2. washwas washed with brine
  3. dry with materialThe organic solution was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resultant residue was purified via silica gel chromatography
  7. washeluting with 0-5% methanol in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-2b03cb4ca50e48338d4ec91d3797ccbd
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08940765B2

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