Triethylamine → N-{3-[8-(2,6-difluorophenyl)-2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methylphenyl}-2-thiophenecarboxamide

HRID 222942Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 222942
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:29])=[C:6]([C:8]2[C:9]3[CH:19]=[CH:18][C:17](=[O:20])[N:16]([C:21]4[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=4[F:28])[C:10]=3[N:11]=[C:12]([S:14][CH3:15])[N:13]=2)[CH:7]=1.CCN(CC)CC.[S:37]1[CH:41]=[CH:40][CH:39]=[C:38]1[C:42](Cl)=[O:43]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[F:27][C:26]1[CH:25]=[CH:24][CH:23]=[C:22]([F:28])[C:21]=1[N:16]1[C:10]2[N:11]=[C:12]([S:14][CH3:15])[N:13]=[C:8]([C:6]3[CH:7]=[C:2]([NH:1][C:42]([C:38]4[S:37][CH:41]=[CH:40][CH:39]=4)=[O:43])[CH:3]=[CH:4][C:5]=3[CH3:29])[C:9]=2[CH:19]=[CH:18][C:17]1=[O:20]

Komponenten

6

Edukt 3

HCID 8471TriethylamineHCID 789282-Thiophenecarbonyl chlorideHCID 592126794-(5-amino-2-methylphenyl)-8-(2,6-difluorophenyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one

Produkt 1

HCID 11948285N-{3-[8-(2,6-difluorophenyl)-2-(methylthio)-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-4-yl]-4-methylphenyl}-2-thiophenecarboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 4-(5-amino-2-methylphenyl)-8-(2,6-difluorophenyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one (411.0 mg, 1.0 mmol) in CH2Cl2 (10 mL) at 0° C. was added Et3N (200.0 mg, 2.0 mmol, 2.0 eq), DMAP (5.0 mg, 0.2 mmol, 0.2 eq) and 2-thiophenecarbonyl chloride (292.0 mg, 2.0 mmol, 2.0 eq). After addition the reaction mixture was stirred for about 14 h at ambient temperature. The mixture was concentrated and mixed with H2O (5.0 mL) and EtOAc (20.0 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (3×15 mL). The combined organic phases were washed with saturated aq. NaCl solution, dried over Na2SO4, filtered, and concentrated. Purification via a CombiFlash system (hexane:EtOAc; 4:1) then afforded the title compound: LC-MS m/z 521 (M+H)+, 2.57 min (ret time).

Aufarbeitung

  1. additionAfter addition the reaction mixture
  2. concentrationThe mixture was concentrated
  3. additionmixed with H2O (5.0 mL) and EtOAc (20.0 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with EtOAc (3×15 mL)
  6. washThe combined organic phases were washed with saturated aq. NaCl solution
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification via a CombiFlash system (hexane:EtOAc; 4:1)

Quellen und Nachweise

ORD-Eintrag
ord-1d44f9da67b24af0a55f9c66657ae00e
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08207176B2

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