Cesium carbonate → 4-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-5-methoxy-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester

HRID 448571

Reaktionsgleichung

Reaktionsgleichung von HRID 448571
[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18](Cl)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:29][S:30]([C:33]1[CH:34]=[C:35]2[C:39](=[CH:40][CH:41]=1)[NH:38][CH2:37][CH2:36]2)(=[O:32])=[O:31].F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>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].O1CCOCC1>[CH:1]([O:4][C:5]([N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[C:19]([O:20][CH3:21])=[C:18]([N:38]3[C:39]4[C:35](=[CH:34][C:33]([S:30]([CH3:29])(=[O:32])=[O:31])=[CH:41][CH:40]=4)[CH2:36][CH2:37]3)[N:17]=[CH:16][N:15]=2)[CH2:9][CH2:8]1)=[O:6])([CH3:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 27361365-(Methanesulfonyl)-2,3-dihydro-1H-indoleHCID 51050526Isopropyl 4-[(6-chloro-5-methoxypyrimidin-4-yl)oxy]piperidine-1-carboxylate

Produkt 1

HCID 252611484-[6-(5-Methanesulfonyl-2,3-dihydro-indol-1-yl)-5-methoxy-pyrimidin-4-yloxy]-piperidine-1-carboxylic acid isopropyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 312751,4-DioxaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

A mixture of 8a (49 mg, 0.15 mmol), cesium carbonate (0.11 g, 2 eq), 5-Methanesulfonyl-2,3-dihydro-1H-indole (35 mg, 1.2 eq), tris(dibenzylideneacetone)-dipalladium (31 mg, 0.1 eq), tri-t-butylphosphonium tetrafluoroborate (37 mg, 0.8 eq) and dioxane (1.5 mL) was heated at 90° C. for 4 h. The mixture cooled to room temperature, dioxane was added and the mixture was filtered and washed with DCM. The filtrate was concentrated under a stream of nitrogen and the residue was taken up in 1 mL of THF and was purified by preparative HPLC to afford 8-1; LCMS 491.2 (MH+), tR=5.35 (Method 6). EC50: 201 nM.

Aufarbeitung

  1. temperatureThe mixture cooled to room temperature
  2. filtrationthe mixture was filtered
  3. washwashed with DCM
  4. concentrationThe filtrate was concentrated under a stream of nitrogen
  5. customwas purified by preparative HPLC
  6. customto afford 8-1

Quellen und Nachweise

ORD-Eintrag
ord-653be0dfc5924825b24740bb09feb911
Quelldatensatz
uspto-grants-2013_07
Patentnummer
US08481731B2

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