Toluene → N-(4-(2-(4-carbamoylphenyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

HRID 1676305Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676305
[C:1]([C:4]1[CH:9]=[CH:8][C:7](B(O)O)=[CH:6][CH:5]=1)(=[O:3])[NH2:2].[F:13][C:14]1[CH:15]=[C:16]([N:31]([C:40]2[CH:45]=[CH:44][C:43]([F:46])=[CH:42][CH:41]=2)[C:32]([C:34]2([C:37]([NH2:39])=[O:38])[CH2:36][CH2:35]2)=[O:33])[CH:17]=[CH:18][C:19]=1[O:20][C:21]1[CH:26]=[CH:25][N:24]=[C:23]2[CH:27]=[C:28](I)[S:29][C:22]=12.C([O-])([O-])=O.[Cs+].[Cs+].C1(C)C=CC=CC=1>O.CCO>[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:28]2[S:29][C:22]3[C:23](=[N:24][CH:25]=[CH:26][C:21]=3[O:20][C:19]3[CH:18]=[CH:17][C:16]([N:31]([C:40]4[CH:41]=[CH:42][C:43]([F:46])=[CH:44][CH:45]=4)[C:32]([C:34]4([C:37]([NH2:39])=[O:38])[CH2:36][CH2:35]4)=[O:33])=[CH:15][C:14]=3[F:13])[CH:27]=2)=[CH:6][CH:5]=1)(=[O:3])[NH2:2]

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 10796Cesium carbonateHCID 27378114-Aminocarbonylphenylboronic acidHCID 67347909N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Produkt 1

HCID 67347374N-(4-(2-(4-carbamoylphenyl)thieno[3,2-b]pyridin-7-yloxy)-3-fluorophenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamideAusbeute 13 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A sealable vial, was charged with 4-carbamoylphenylboronic acid (0.0312 g, 0.189 mmol), N-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (Example 12, Step A, 0.100 g, 0.0947 mmol), Cs2CO3 (0.0309 g, 0.0947 mmol), toluene (2 mL) and EtOH (1 mL). Under nitrogen Pd(PPh3)4 (0.00547 g, 0.00473 mmol) was added and the reaction heated to 80° C. for 18 hours. The mixture was then cooled to room temperature, diluted with water (20 mL), and extracted with ethyl acetate (30 mL) and MeOH (2 mL). The organics were dried over sodium sulfate, filtered and concentrated to get crude product. The crude product was purified by reverse phase C-18 column chromatography to get product (6.9 mg, 13%) as a white solid. LRMS (esi+) 585 m/z (M+1) detected. 1H NMR (d6-DMSO, 400 MHz) δ 8.48 (d, J=6 Hz, 1H), 7.96 (m, 5H), 7.87 (m, 1H), 7.57 (m, 2H), 7.37 (m, 2H), 7.07 (t, J=9.0 Hz, 2H), 6.65 (d, J=6 Hz, 1H), 1.64 (s, 4H).

Aufarbeitung

  1. additionUnder nitrogen Pd(PPh3)4 (0.00547 g, 0.00473 mmol) was added
  2. temperatureThe mixture was then cooled to room temperature
  3. extractionextracted with ethyl acetate (30 mL) and MeOH (2 mL)
  4. dry with materialThe organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto get crude product
  8. customThe crude product was purified by reverse phase C-18 column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-711cb9e2670e4ac38c69a34e63ac1aa5
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003662B2

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