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Butyl vinyl ether → tert-Butyl 4-(6-((6-(1-Butoxyethenyl)-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido(2,3-d)pyrimidin-2-yl)amino)-pyridin-3-yl)-piperazine-1-carboxylate

HRID 1393619
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1393619
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:15]=[N:16][C:17]([NH:20][C:21]3[N:22]=[CH:23][C:24]4[C:30]([CH3:31])=[C:29]([C:32]([O:34][CH2:35][CH3:36])=[CH2:33])[C:28](=[O:37])[N:27]([CH:38]5[CH2:42][CH2:41][CH2:40][CH2:39]5)[C:25]=4[N:26]=3)=[CH:18][CH:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:43](OCCCC)=[CH2:44].C(N(C(C)C)CC)(C)C>ClCCl.[Pd](Cl)Cl.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[CH-]1C=CC=C1.[Fe+2].C(O)CCC>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:15]=[N:16][C:17]([NH:20][C:21]3[N:22]=[CH:23][C:24]4[C:30]([CH3:31])=[C:29]([C:32]([O:34][CH2:35][CH2:36][CH2:43][CH3:44])=[CH2:33])[C:28](=[O:37])[N:27]([CH:38]5[CH2:39][CH2:40][CH2:41][CH2:42]5)[C:25]=4[N:26]=3)=[CH:18][CH:19]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

6

Edukt 3

HCID 8108Butyl vinyl etherHCID 81531DiisopropylethylamineHCID 112731704-{6-[8-Cyclopentyl-6-(1-ethoxy-vinyl)-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino]-pyridin-3-yl}-piperazine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 44248250tert-Butyl 4-(6-((6-(1-Butoxyethenyl)-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido(2,3-d)pyrimidin-2-yl)amino)-pyridin-3-yl)-piperazine-1-carboxylate
Ausbeute 75,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178478481HCID 178478481, VerbindungKatalysatorHCID 2631-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
95 °C

Versuchsvorschrift

A 5-L, three-necked, round-bottomed flask, equipped with a mechanical stirrer, a thermocouple, and a nitrogen inlet/outlet vented through a silicone oil bubbler was placed under a nitrogen atmosphere and charged with 4-[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester (300 g, 0.51 mol, prepared as in Example 2), butyl vinyl ether (154 g, 1.54 mol, ALDRICH), n-butanol (1.5 L, ALDRICH), and diisopropyl ethylamine (107 mL, 0.62 mol, ALDRICH). The slurry was placed under approximately 50 Torr vacuum and then refilled with nitrogen 3 times. To this was added 8.3 g (0.01 mol) bis-(diphenylphosphinoferrocene) palladium dichloride dichloromethane (JOHNSON MATTHEY, Lot 077598001) and the resulting slurry was purged an additional three times as described above. The mixture was then heated to 95° C. and stirred for 20 h. The resulting thin red slurry was diluted with 2 L of heptane and cooled to approximately 5° C. At this temperature, 400 mL saturated aqueous potassium carbonate was added and the mixture was filtered and rinsed with 250 mL of heptane. After drying in an oven for 16 h at 45° C., 231.7 g (75% yield) of the title compound was obtained as a yellow solid.

Aufarbeitung

  1. additionrefilled with nitrogen 3 times
  2. customthe resulting slurry was purged an additional three times
  3. additionThe resulting thin red slurry was diluted with 2 L of heptane
  4. temperaturecooled to approximately 5° C
  5. additionAt this temperature, 400 mL saturated aqueous potassium carbonate was added
  6. filtrationthe mixture was filtered
  7. washrinsed with 250 mL of heptane
  8. customAfter drying in an oven for 16 h at 45° C.

Quellen und Nachweise

ORD-Eintrag
ord-71d7af4ace9d40cc9a958a26b1c9802a
Quelldatensatz
uspto-grants-2008_03
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US07345171B2

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