Sodium Carbonate → HCID 178499303, Verbindung

HRID 73212Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 73212
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.[CH3:11][O:12][C:13]([C:15]1[S:16][C:17](I)=[CH:18][C:19]=1[N:20]([C:28]([C@H:30]1[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]1)=[O:29])[CH:21]1[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]1)=[O:14].C1(C)C=CC=CC=1.CO.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:11][O:12][C:13]([C:15]1[S:16][C:17]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[CH:18][C:19]=1[N:20]([C:28]([C@H:30]1[CH2:31][CH2:32][C@H:33]([CH3:36])[CH2:34][CH2:35]1)=[O:29])[CH:21]1[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]1)=[O:14]

Komponenten

7

Edukt 4

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 21867641Toluene methanolHCID 178499357HCID 178499357, Verbindung

Produkt 1

HCID 178499303HCID 178499303, VerbindungAusbeute 72,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

To the mixture of 4-chlorophenylboronic acid (46.9 mg, 0.3 mmol) and 5-iodo-3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid methyl ester (50 mg, 0.099 mmol), from step 5, in 5:1 mixture of toluene/MeOH (2.0 mL) was added a solution of Pd(PPh3)4 (12.0 mg, 0.01 mmol, 10 mol %) in toluene (1.0 mL) followed by aqueous 2M Na2CO3 solution (0.1 mL, 0.2 mmol). The resultant reaction mixture was heated at 70° C. for 16 h, cooled to room temperature, filtered off through MgSO4 and washed with EtOAc. Evaporation of the solvent and purification of the residue over preparative TLC (1 mm, 60 A°) using DCM/CHCl3/MeOH/Et3N (100:90:16:1) as an eluent furnished 5-(4-chloro-phenyl)-3-[(trans-4-methyl-cyclohexanecarbonyl)-(1-methyl-piperidin-4-yl)-amino]-thiophene-2-carboxylic acid methyl ester (35.0 mg, 71.5% yield). NMR 1H (CDCl3, 400 MHz): 7.53 (d, J=8.3, 2H), 7.4 (d, J=8.5, 2H), 7.0 (s, 1H), 4.67-4.58 (m, 1H), 3.84 (s, 3H), 2.82-2.64 (m, 1H), 2.2 (s, 3H), 2.14-1.35 (m), 0.763 (d, J=6.6, 3H), 0.76-0.56 (m, 2H).

Aufarbeitung

  1. customThe resultant reaction mixture
  2. temperaturecooled to room temperature
  3. filtrationfiltered off through MgSO4
  4. washwashed with EtOAc
  5. customEvaporation of the solvent and purification of the residue over preparative TLC (1 mm, 60 A°)

Quellen und Nachweise

ORD-Eintrag
ord-996b89c1390d4703aa19a13933425eb8
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08829030B2

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