Trifluoroacetic acid → N-[6-(3-chloro-thiophene-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-ethoxy-benzamide

HRID 1444596

Reaktionsgleichung

Reaktionsgleichung von HRID 1444596
FC(F)(F)C(O)=O.C(O[C:13]([N:15]1[CH2:36][CH2:35][C:18]2[N:19]=[C:20]([NH:23][C:24](=[O:34])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[O:31][CH2:32][CH3:33])[N:21]=[CH:22][C:17]=2[CH2:16]1)=[O:14])(C)(C)C.CCN(C(C)C)C(C)C.[Cl:46][C:47]1[CH:51]=[CH:50][S:49][C:48]=1C(O)=O.CCN=C=NCCCN(C)C.C1C=NC2N(O)N=NC=2C=1>C(Cl)Cl>[Cl:46][C:47]1[CH:51]=[CH:50][S:49][C:48]=1[C:13]([N:15]1[CH2:36][CH2:35][C:18]2[N:19]=[C:20]([NH:23][C:24](=[O:34])[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[O:31][CH2:32][CH3:33])[N:21]=[CH:22][C:17]=2[CH2:16]1)=[O:14]

Komponenten

8

Edukt 6

HCID 6422Trifluoroacetic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 7012693-Chlorothiophene-2-carboxylic acidHCID 686797542-(2-ethoxy-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester

Produkt 1

HCID 68679116N-[6-(3-chloro-thiophene-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-ethoxy-benzamideAusbeute 51 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Trifluoroacetic acid 3.6 ml (49 mmol) was added to a solution of 2-(2-ethoxy-benzoylamino)-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-6-carboxylic acid tert-butyl ester 300 mg (0.753 mmol) in CH2Cl2 (10 ml) under nitrogen as inert gas and stirring was performed for 2 h at RT. After removal of the solvent, the intermediate (2-ethoxy-N-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide trifluoroacetate) was dissolved in CH2Cl2 (10 ml) and DIPEA 225 μl and 3-chlorothiophene-2-carboxylic acid 129 mg (0.791 mmol) were added. After cooling the reaction mixture to 0° C., EDCI 158 mg (0.828 mmol) and HOAt 15 mg (0.11 mmol) were added. The reaction mixture was stirred for 1 h at 0° C. and then overnight at RT. After removal of the solvent, purification was performed by means of column chromatography and the product N-[6-(3-chloro-thiophene-2-carbonyl)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl]-2-ethoxy-benzamide 170 mg (0.38 mmol, 51% of theoretical) was obtained.

Aufarbeitung

  1. customAfter removal of the solvent
  2. dissolutionthe intermediate (2-ethoxy-N-(5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)-benzamide trifluoroacetate) was dissolved in CH2Cl2 (10 ml)
  3. stirringThe reaction mixture was stirred for 1 h at 0° C.
  4. customovernight
  5. customat RT
  6. customAfter removal of the solvent, purification

Quellen und Nachweise

ORD-Eintrag
ord-44f62f91c4b04d87b1627b7936db4ad9
Quelldatensatz
uspto-grants-2010_02
Patentnummer
US07662828B2

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