Diisopropylamine → 3-fluoro-N-(4-{[2-(methylthio)pyrimidin-4-yl]oxy}-1-naphthyl)-5-morpholin-4-ylbenzamide

HRID 1171271Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1171271
[CH3:1][S:2][C:3]1[N:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([NH:20][C:21](=[O:27])OC(C)(C)C)=[CH:12][CH:11]=2)[CH:6]=[CH:5][N:4]=1.[F:28][CH:29]1COCC(C2C(C(O)=O)=CC=CC=2)N1.[Cl-].ClC1N(C)[CH2:49][CH2:48][NH+]1C.[CH:53]([NH:56][CH:57]([CH3:59])[CH3:58])([CH3:55])C.[O:60]1[CH2:65][CH2:64]OCC1>Cl.C(Cl)Cl>[F:28][C:29]1[CH:48]=[C:49]([CH:58]=[C:57]([N:56]2[CH2:64][CH2:65][O:60][CH2:55][CH2:53]2)[CH:59]=1)[C:21]([NH:20][C:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:10]([O:9][C:7]2[CH:6]=[CH:5][N:4]=[C:3]([S:2][CH3:1])[N:8]=2)=[CH:11][CH:12]=1)=[O:27]

Komponenten

8

Edukt 5

HCID 7912DiisopropylamineHCID 312751,4-DioxaneHCID 109867151H-Imidazolium, 2-chloro-4,5-dihydro-1,3-dimethyl-, chlorideHCID 59553280t-Butyl(4-{[2-(methylthio)pyrimidin-4-yl]oxy}-1-naphthyl)carbamateHCID 667380893-Fluoro-5-morpholinebenzoic acid

Produkt 1

HCID 595530703-fluoro-N-(4-{[2-(methylthio)pyrimidin-4-yl]oxy}-1-naphthyl)-5-morpholin-4-ylbenzamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 313Hydrochloric AcidLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of t-butyl (4-{[2-(methylthio) pyrimidin-4-yl]oxy}-1-naphthyl)carbamate (1.0 g, 2.61 mmol) in 4.0 M HCl in dioxane (10 ml) is stirred at room temperature for 1 h. The mixture is then evaporated to dryness. The residue is then dissolved in CH2Cl2 (5 ml) containing diisopropylamine (1.0 ml). To this mixture is added a solution of 3-fluoro-5-morpholinebenzoic acid (0.70 g, 3.13 mmol), 2-chloro-1,3-dimethylimidazolinium chloride (0.525 g, 3.13 mmol) and diisopropylamine (1.27 ml) in CH2Cl2 (10 ml) at room temperature. The mixture is stirred at room temperature overnight and then washed with saturated NaHCO3 solution, brine, dried over Na2SO4 and concentrated. The residue is purified by column chromatography on silica gel (10-60% EtOAc in hexane) to give 3-fluoro-N-(4-{[2-(methylthio)pyrimidin-4-yl]oxy}-1-naphthyl)-5-morpholin-4-ylbenzamide as an off-white solid (0.75 g). Mp: 189-190° C.; 1H NMR (300 MHz, CDCl3) δ 2.29 (s, 3H), 3.25 (t, J=4.8 Hz, 4H), 3.87 (t, J=5.1Hz, 4H), 6.53 (d, J=6.0 Hz, 1H), 6.75-6.80 (m, 1H), 7.07 (d, J=8.4 Hz, 1H), 7.30-7.33 (m, 2H), 7.49-7.56 (m, 2H), 7.89-7.97 (m, 3H), 8.16 (s, 1H), 8.36 (d, J=5.7 Hz, 1H); MS: 491 (M+1).

Aufarbeitung

  1. customThe mixture is then evaporated to dryness
  2. dissolutionThe residue is then dissolved in CH2Cl2 (5 ml)
  3. additioncontaining diisopropylamine (1.0 ml)
  4. washwashed with saturated NaHCO3 solution, brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue is purified by column chromatography on silica gel (10-60% EtOAc in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-320ab1a67d0446f8ace032408b521611
Quelldatensatz
uspto-grants-2010_11
Patentnummer
US07829560B2

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