Lithium diisopropylamide → HCID 70977892, Verbindung

HRID 2402392Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2402392
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[S:12][CH:11]=[N:10][CH:9]=2)[N:5]=[C:4]([NH:13][C:14]2[CH:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=2)[CH:3]=1.C([N-]C(C)C)(C)C.[Li+].[O:32]=[C:33]1[CH2:42][CH2:41][CH2:40][C:39]2[CH:38]=[C:37]([C:43]([O:45][CH3:46])=[O:44])[CH:36]=[CH:35][C:34]1=2>C1COCC1>[OH:32][C:33]1([C:11]2[S:12][C:8]([C:6]3[CH:7]=[C:2]([CH3:1])[CH:3]=[C:4]([NH:13][C:14]4[CH:19]=[C:18]([C:20]([F:23])([F:21])[F:22])[CH:17]=[CH:16][N:15]=4)[N:5]=3)=[CH:9][N:10]=2)[CH2:42][CH2:41][CH2:40][C:39]2[CH:38]=[C:37]([C:43]([O:45][CH3:46])=[O:44])[CH:36]=[CH:35][C:34]1=2

Komponenten

5

Edukt 3

HCID 2724682Lithium diisopropylamideHCID 15309116Methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylateHCID 709773814-methyl-6-(1,3-thiazol-5-yl)-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine

Produkt 1

HCID 70977892HCID 70977892, VerbindungAusbeute 89,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a solution of 4-methyl-6-(1,3-thiazol-5-yl)-N-[4-(trifluoromethyl)pyridin-2-yl]pyridin-2-amine (500 mg, 1.487 mmol) in THF (5.9 mL) under argon at −78° C. was added lithium diisopropylamide (2.0 M in tetrahydrofuran, 2.2 mL, 4.46 mmol), and the resulting mixture was stirred as such for 30 minutes. To this mixture was added a solution of methyl 5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate (379 mg, 1.858 mmol) in THF (2 mL), and the reaction was then allowed to warm to rt over a period of 2 h. After stirring for an additional 14 h, the reaction was quenched with methanol (10 mL) and directly concentrated. Chromatography on silica gel (dichloromethane-methanol) afforded (rac)-methyl 5-hydroxy-5-[5-(4-methyl-6-{[4-(trifluoromethyl)pyridin-2-yl]amino}pyridin-2-yl)-1,3-thiazol-2-yl]-5,6,7,8-tetrahydronaphthalene-2-carboxylate as a light brown solid (718.0 mg, 1.328 mmol, 89% yield). MS ESI calcd for C27H23F3N4O3S [M+H]+ 541, found 541. 1H NMR (500 MHz, DMSO) δ 10.20 (s, 1H), 8.63 (s, 1H), 8.48 (d, J=5.0 Hz, 1H), 8.23 (s, 1H), 7.74 (s, 1H), 7.69 (d, J=8.2 Hz, 1H), 7.36 (s, 1H), 7.23-7.17 (m, 2H), 7.09 (s, 1H), 6.63 (s, 1H), 3.82 (s, 3H), 2.92-2.85 (m, 2H), 2.33-2.30 (m, 4H), 2.15-2.09 (m, 1H), 2.02-1.88 (m, 2H) ppm.

Aufarbeitung

  1. stirringAfter stirring for an additional 14 h
  2. customthe reaction was quenched with methanol (10 mL)
  3. concentrationdirectly concentrated

Quellen und Nachweise

ORD-Eintrag
ord-f13358e9426a41ebb1c48b4d6726d248
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08796310B2

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