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Cesium carbonate → tert-Butyl (35)-4-(6-{[5-(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-3-(hydroxymethyl)pyridin-4-yl)-2-methoxypyridin-3-yl]amino}pyridin-3-yl)-3-methylpiperazine-1-carboxylate

HRID 1411977
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1411977
Cl[C:2]1[CH:3]=[C:4]([NH:10][C:11]2[N:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][C@@H:18]3[CH3:30])=[CH:13][CH:12]=2)[C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C([O:34][CH2:35][C:36]1[C:37]([N:51]2[CH2:62][CH2:61][N:60]3[C:53](=[CH:54][C:55]4[CH2:56][C:57]([CH3:64])([CH3:63])[CH2:58][C:59]=43)[C:52]2=[O:65])=[N:38][CH:39]=[CH:40][C:41]=1B1OC(C)(C)C(C)(C)O1)(=O)C.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C([O-])([O-])=O.[Cs+].[Cs+].O.[OH-].[Li+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.O1CCOCC1>[CH3:63][C:57]1([CH3:64])[CH2:56][C:55]2[CH:54]=[C:53]3[N:60]([CH2:61][CH2:62][N:51]([C:37]4[C:36]([CH2:35][OH:34])=[C:41]([C:2]5[CH:3]=[C:4]([NH:10][C:11]6[N:16]=[CH:15][C:14]([N:17]7[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:19][C@@H:18]7[CH3:30])=[CH:13][CH:12]=6)[C:5]([O:8][CH3:9])=[N:6][CH:7]=5)[CH:40]=[CH:39][N:38]=4)[C:52]3=[O:65])[C:59]=2[CH2:58]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

9

Edukt 5

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 168937Lithium hydroxide, monohydrateHCID 86684013tert-Butyl (3S)-4-{6-[(5-chloro-2-methoxypyridin-3-yl)amino]pyridin-3-yl}-3-methylpiperazine-1-carboxylateHCID 86684419(2-(7,7-dimethyl-1-oxo-3,4,7,8-tetrahydro-1H-cyclopenta[4,5]pyrrolo[1,2-a]pyrazin-2(6H)-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl)methyl acetate

Produkt 1

HCID 86726161tert-Butyl (35)-4-(6-{[5-(2-{4,4-Dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}-3-(hydroxymethyl)pyridin-4-yl)-2-methoxypyridin-3-yl]amino}pyridin-3-yl)-3-methylpiperazine-1-carboxylateAusbeute 27,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittel2×HCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
110 °C

Versuchsvorschrift

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 271a (650 mg, 1.50 mmol), {3-[(acetyloxy)methyl]-2-{4,4-dimethyl-9-oxo-1,10-diazatricyclo[6.4.0.02,6]dodeca-2(6),7-dien-10-yl}pyridin-4-yl}boronic acid 199e (1.79 g, 4.5 mmol), Pd2(dba)3 (137.2 mg, 0.15 mmol), P(cy)3(167.4 mg, 0.60 mmol), Cs2CO3 (978 mg, 3.0 mmol), dioxane (20 mL), and water (0.5 mL). After three cycles of vacuum/argon flush, the mixture was heated at 110° C. for 16 h. After this time the reaction was cooled to room temperature. Lithium hydroxide monohydrate (1.89 g, 45 mmol) and water (2.0 mL) were added. The resulting mixture was stirred at 45° C. for 4 h. It was then filtered and the filtrate was evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 3:1 ethyl acetate/petroleum ether to afford 271b (290 mg, 27%) as a yellow solid. MS-ESI: [M+H]+ 709.3

Aufarbeitung

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperatureAfter this time the reaction was cooled to room temperature
  4. filtrationIt was then filtered
  5. customthe filtrate was evaporated under reduced pressure
  6. customThe residue was purified by silica-gel column chromatography
  7. washeluting with 3:1 ethyl acetate/petroleum ether

Quellen und Nachweise

ORD-Eintrag
ord-cf4166f282e84810b6f8dee99d78f755
Quelldatensatz
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08921353B2

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