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Sodium Carbonate → Methyl 2-[4-({[2-[2-(2,3-difluorophenyl)ethyl]-4-oxopyrido[2,3-d]pyrimidin-1(4H)-yl]-acetyl}{[4'-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoate

HRID 1855637
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1855637
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]1[N:16]([CH2:17][C:18](O)=[O:19])[C:15]2[N:21]=[CH:22][CH:23]=[CH:24][C:14]=2[C:13](=[O:25])[N:12]=1.[CH3:26][C:27]([N:33]1[CH2:38][CH2:37][CH:36]([NH:39][CH2:40][C:41]2[CH:46]=[CH:45][C:44]([C:47]3[CH:52]=[CH:51][C:50]([C:53]([F:56])([F:55])[F:54])=[CH:49][CH:48]=3)=[CH:43][CH:42]=2)[CH2:35][CH2:34]1)([CH3:32])[C:28]([O:30][CH3:31])=[O:29].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(=O)([O-])[O-].[Na+].[Na+]>C(OCC)C.C1COCC1.CN(C=O)C>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:9][CH2:10][C:11]1[N:16]([CH2:17][C:18]([N:39]([CH2:40][C:41]2[CH:46]=[CH:45][C:44]([C:47]3[CH:48]=[CH:49][C:50]([C:53]([F:55])([F:56])[F:54])=[CH:51][CH:52]=3)=[CH:43][CH:42]=2)[CH:36]2[CH2:37][CH2:38][N:33]([C:27]([CH3:26])([CH3:32])[C:28]([O:30][CH3:31])=[O:29])[CH2:34][CH2:35]2)=[O:19])[C:15]2[N:21]=[CH:22][CH:23]=[CH:24][C:14]=2[C:13](=[O:25])[N:12]=1
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 5

HCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11187030[2-[2-(2,3-difluorophenyl)ethyl]-4-oxopyrido[2,3-d]pyrimidin-1(4H)-yl]acetic acidHCID 59264602HCID 59264602, Verbindung

Produkt 1

HCID 24771862Methyl 2-[4-({[2-[2-(2,3-difluorophenyl)ethyl]-4-oxopyrido[2,3-d]pyrimidin-1(4H)-yl]-acetyl}{[4'-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]-2-methylpropanoateAusbeute 78,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 21868444Ether tetrahydrofuranLösungsmittel

Versuchsvorschrift

A mixture of [2-[2-(2,3-difluorophenyl)ethyl]-4-oxopyrido[2,3-d]pyrimidin-1(4H)-yl]acetic acid (Int. D1) (20.7 g, 1.3 equiv), methyl 2-methyl-2-[4-({[4′-(trifluoromethyl)-4-biphenylyl]methyl}amino)-1-piperidinyl]propanoate (Int. B1) (20.0 g, 1.3 equiv), DIPEA (24.0 ml, 3 equiv) and DMF (184 ml) was mechanically stirred, then HATU (27.1 g, 1.5 equiv) was added in one portion and stirring continued for 2 h. The reaction mixture was partioned between diethyl ether/THF (1:1) and sodium carbonate (1M, excess). The organic layer was washed with water and brine, dried and evaporated. Chromatography was run sequentially on three silica columns (firstly 3:1 EtOAc/hexanes; secondly 2% MeOH in DCM; thirdly 1:1 EtOAc/hexanes to 100% EtOAc). Product fractions were evaporated to obtain the desired product as an amorphous pink solid (27.5 g).

Aufarbeitung

  1. stirringstirring
  2. washThe organic layer was washed with water and brine
  3. customdried
  4. customevaporated
  5. customProduct fractions were evaporated

Quellen und Nachweise

ORD-Eintrag
ord-1b1a9176f3b54ea6bef23eb764885a71
Quelldatensatz
uspto-grants-2015_02
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08962633B2

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