Thionyl Chloride → 7-[(2E)-4-Chlorobut-2-enoyl]-N-(3-chloro-4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amine

HRID 38545

Reaktionsgleichung

Reaktionsgleichung von HRID 38545
Br[CH2:2]/[CH:3]=[CH:4]/[C:5]([OH:7])=O.S(Cl)([Cl:10])=O.[Cl:12][C:13]1[CH:14]=[C:15]([NH:20][C:21]2[C:22]3[C:29]4[CH2:30][CH2:31][NH:32][CH2:33][C:28]=4[S:27][C:23]=3[N:24]=[CH:25][N:26]=2)[CH:16]=[CH:17][C:18]=1[F:19].CCN(C(C)C)C(C)C>CN(C=O)C.O.C(OCC)(=O)C>[Cl:10][CH2:2]/[CH:3]=[CH:4]/[C:5]([N:32]1[CH2:31][CH2:30][C:29]2[C:22]3[C:21]([NH:20][C:15]4[CH:16]=[CH:17][C:18]([F:19])=[C:13]([Cl:12])[CH:14]=4)=[N:26][CH:25]=[N:24][C:23]=3[S:27][C:28]=2[CH2:33]1)=[O:7]

Komponenten

8

Edukt 4

HCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 64364114-Bromocrotonic acidHCID 58116889(3-Chloro-4-fluoro-phenyl)-(5,6,7,8-tetrahydro-9-thia-1,3,7-triaza-fluoren-4-yl)-amine

Produkt 1

HCID 581169827-[(2E)-4-Chlorobut-2-enoyl]-N-(3-chloro-4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amineAusbeute 57,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
-10 °C

Versuchsvorschrift

(2E)-4-Bromobut-2-enoic acid (1.48 g, 7.17 mmol) was stirred in thionylchloride (10 mL, 137 mmol) for 4 h. The mixture was then concentrated in vacuo. Twice, toluene was added and again removed in vacuo. The residue was dissolved in dichloromethane (14 mL). This solution was added to a solution of N-(3-chloro-4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4′,3′:4,5]thieno[2,3-d]-pyrimidin-4-amine from Example 12A (2.00 g, 5.97 mmol) and DIPEA (1.93 g, 14.9 mmol) in DMF (35 mL) at −10° C. The mixture was stirred for 1.5 h at −10° C. and subsequently for 15 h at rt. The mixture was then diluted with water. Ethyl acetate was added, and the precipitate was collected by suction filtration to yield 1.50 g of a solid, which was identified by LC/MS as a mixture of the bromo- and chloro-allylic compound. It was used in the next step without further purification or separation.

Aufarbeitung

  1. concentrationThe mixture was then concentrated in vacuo
  2. additionTwice, toluene was added
  3. customagain removed in vacuo
  4. dissolutionThe residue was dissolved in dichloromethane (14 mL)
  5. filtrationthe precipitate was collected by suction filtration

Quellen und Nachweise

ORD-Eintrag
ord-c13471071ba14e3999b8e74b4579f7b3
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524722B2

Verknüpfte Notizen

Wird geladen…