7-Chloro-2-iodothieno[3,2-b]pyridine → 5-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

HRID 1676337Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1676337
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:10](=[O:23])[N:11]([CH3:22])[C:12]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:13][CH:14]=2)[CH:5]=[CH:6][C:7]=1[OH:8].Cl[C:25]1[CH:30]=[CH:29][N:28]=[C:27]2[CH:31]=[C:32]([I:34])[S:33][C:26]=12>CN(C1C=CN=CC=1)C.BrC1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:10](=[O:23])[N:11]([CH3:22])[C:12]([NH:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[N:13][CH:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:25]1[CH:30]=[CH:29][N:28]=[C:27]2[CH:31]=[C:32]([I:34])[S:33][C:26]=12

Komponenten

5

Edukt 2

HCID 177504007-Chloro-2-iodothieno[3,2-b]pyridineHCID 673501215-(3-fluoro-4-hydroxyphenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

Produkt 1

HCID 673484955-(3-fluoro-4-(2-iodothieno[3,2-b]pyridin-7-yloxy)phenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 7961BromobenzeneLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

A suspension of 5-(3-fluoro-4-hydroxyphenyl)-3-methyl-2-(phenylamino)pyrimidin-4(3H)-one (0.113 g, 0.266 mmol), 7-chloro-2-iodothieno[3,2-b]pyridine (0.075 g, 0.254 mmol; prepared according to the procedure of Ragan, J. A. Org. Proc. Res. 2003, 7, 676) and DMAP (0.003 g, 0.025 mmol) in bromobenzene (3 mL) was stirred under nitrogen. The reaction mixture was allowed to stir for 7 days at 150° C. and then for 2 days at room temperature. The reaction was concentrated in vacuo to remove as much bromobenzene as possible. The resulting gummy brown residue was dissolved in CH2Cl2 and then EtOAc was added to yield a dark brown solid precipitate that was filtered and washed with EtOAc. The filtrate, which contained the desired product, was concentrated and purified by flash column chromatography, eluting with 10:1 CH2Cl2/MeOH. Product containing fractions were pooled and concentrated to yield (0.020 mg) of the desired product. Impure fractions were pooled, concentrated and repurified by flash column chromatography, eluting with 20:1 CH2Cl2/MeOH. The product isolated from the two purifications were combined to yield the desired product (39 mg; 27%) as a yellow solid. LRMS (APCI pos) m/e 571 (M+1).

Aufarbeitung

  1. customprepared
  2. waitfor 2 days at room temperature
  3. concentrationThe reaction was concentrated in vacuo
  4. customto remove as much bromobenzene as possible
  5. dissolutionThe resulting gummy brown residue was dissolved in CH2Cl2
  6. additionEtOAc was added
  7. customto yield a dark brown solid precipitate that
  8. filtrationwas filtered
  9. washwashed with EtOAc
  10. concentrationwas concentrated
  11. custompurified by flash column chromatography
  12. washeluting with 10:1 CH2Cl2/MeOH
  13. additionProduct containing fractions
  14. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-1ae0f8d01cea4c5d969eff5d37f6c80f
Quelldatensatz
uspto-grants-2011_08
Patentnummer
US08003662B2

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