Lithium Chloride → 5-(2,5-difluoro-4-(2-(4-(morpholine-4-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

HRID 1676381Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676381
[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16](I)[S:17][C:10]=23)[C:5]([F:19])=[CH:4][C:3]=1[C:20]1[C:21](=[O:34])[N:22]([CH3:33])[C:23]([NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[N:24][CH:25]=1.[N:35]1([C:41]([C:43]2[CH:48]=[CH:47][C:46](B(O)O)=[CH:45][CH:44]=2)=[O:42])[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1.[Cl-].[Li+]>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].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>[F:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[CH:15]=[C:16]([C:46]4[CH:45]=[CH:44][C:43]([C:41]([N:35]5[CH2:40][CH2:39][O:38][CH2:37][CH2:36]5)=[O:42])=[CH:48][CH:47]=4)[S:17][C:10]=23)[C:5]([F:19])=[CH:4][C:3]=1[C:20]1[C:21](=[O:34])[N:22]([CH3:33])[C:23]([NH:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[N:24][CH:25]=1

Komponenten

7

Edukt 3

HCID 433294Lithium ChlorideHCID 2773546[4-(Morpholine-4-carbonyl)phenyl]boronic acidHCID 673481795-(2,5-difluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

Produkt 1

HCID 589495355-(2,5-difluoro-4-(2-(4-(morpholine-4-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 10340Sodium CarbonateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A suspension of 5-(2,5-difluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one (0.0105 g, 0.0178 mmol), 4-(morpholine-4-carbonyl)phenylboronic acid (0.005 g, 0.021 mmol), Pd(PPh3)4 (0.001 g, 0.001 mmol) and lithium chloride (0.003 g, 0.071 mmol) in dioxane (0.5 mL) and 2M aqueous Na2CO3 (0.5 mL) was stirred at 100° C. for 30 minutes. The reaction mixture was cooled to room temperature and then partitioned between EtOAc and H2O. The layers were separated and the aqueous layer was re-extracted with EtOAc (1×). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with 20:1 CH2Cl2/MeOH. The product was obtained (4.5 mg; 39%) as a pale yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.54 (br s, 1H), 7.96 (s, 1H), 7.84-7.77 (m, 3H), 7.57-7.46 (m, 5H), 7.42 (t, 2H), 7.24 (m, 1H), 7.08 (m, 1H), 6.71-6.62 (m, 2H), 3.99-3.40 (m, 8H), 3.68 (s, 3H). LRMS (APCI pos) m/e 652 (M+1).

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between EtOAc and H2O
  3. customThe layers were separated
  4. extractionthe aqueous layer was re-extracted with EtOAc (1×)
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude product was purified by flash column chromatography
  9. washeluting with 20:1 CH2Cl2/MeOH
  10. customThe product was obtained (4.5 mg; 39%) as a pale yellow solid

Quellen und Nachweise

ORD-Eintrag
ord-bfea3d70ee934ecab6fd2e51e2bc9c97
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003662B2

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