Water → (2e)-3-[4-Amino-3-(4-chlorophenyl)thieno[3,2-c]pyridin-7-yl]-n-methylacrylamide

HRID 17123

Reaktionsgleichung

Reaktionsgleichung von HRID 17123
[NH2:1][C:2]1[C:7]2[C:8](Br)=[CH:9][S:10][C:6]=2[C:5](/[CH:12]=[CH:13]/[C:14]([NH:16][CH3:17])=[O:15])=[CH:4][N:3]=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22](B(O)[OH:26])=[CH:21][CH:20]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>COCCOC.O.C(O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.ClCCl>[C:14]([O-:15])(=[O:26])[CH3:13].[NH4+:1].[NH2:1][C:2]1[C:7]2[C:8]([C:22]3[CH:23]=[CH:24][C:19]([Cl:18])=[CH:20][CH:21]=3)=[CH:9][S:10][C:6]=2[C:5](/[CH:12]=[CH:13]/[C:14]([NH:16][CH3:17])=[O:15])=[CH:4][N:3]=1

Komponenten

9

Edukt 4

HCID 962WaterHCID 10796Cesium carbonateHCID 742994-Chlorophenylboronic acidHCID 18450640(2e)-3-(4-Amino-3-bromothieno[3,2-c]pyridin-7-yl)-n-methylacrylamide

Produkt 2

HCID 517165Ammonium AcetateHCID 18450600(2e)-3-[4-Amino-3-(4-chlorophenyl)thieno[3,2-c]pyridin-7-yl]-n-methylacrylamideAusbeute 71,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418476HCID 178418476, VerbindungKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 86587095Dimethoxyethane ethanol waterLösungsmittel

Versuchsvorschrift

A mixture of Example 21B (150 mg, 0.48 mmol), 4-chlorophenylboronic acid (75 mg, 0.48 mmol), PdCl2(PPh3)2 (3 mg) and Cs2CO3 (188 mg) in DME/water/ethanol (70:30:20 mixture, 2 mL) was heated in a sealed vial to 160° C. for 7.5 minutes with stirring in a Smith Synthesizer microwave oven (at 300 W). The reaction was partinioned between water and dichloromethane and the organic layer was concentrated. The residue collected was purified by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size) using a gradient of 10% to 100% acetonitrile:5 mM aqueous ammonium acetate over 8 minutes (10 minute run time) at a flow rate of 40 mL/min to provide 59 mg (36% yield) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 2.73 (d, J=4.7 Hz, 3H), 5.81 (s, 2H), 6.58 (d, J=15.9 Hz, 1H), 7.51 (d, J=8.5 Hz, 2H), 7.58 (d, J=15.9 Hz, 1H), 7.60 (d, J=8.5 Hz, 2H), 7.70 (s, 1H), 8.13 (s, 1H), 8.16 (q, J=4.7 Hz, 1H), MS (ESI(−)) m/e 341.8 (M−H)−.

Aufarbeitung

  1. concentrationthe organic layer was concentrated
  2. customThe residue collected
  3. customwas purified by preparative HPLC on a Waters Symmetry C8 column (25 mm×100 mm, 7 μm particle size)

Quellen und Nachweise

ORD-Eintrag
ord-213f205d2e184c08bd11f97525a9c28d
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07737160B2

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