Cesium carbonate → {3,5-Dichloro-4-[7-fluoro-4-(6-hydroxymethylpyrimidin-4-ylamino)-thiazolo[5,4-c]pyridin-2-yl]phenyl}-carbamic acid tert-butyl ester

HRID 2366320Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2366320
[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[CH:13]=[C:12]([Cl:14])[C:11]([C:15]2[S:16][C:17]3[C:18](Cl)=[N:19][CH:20]=[C:21]([F:24])[C:22]=3[N:23]=2)=[C:10]([Cl:26])[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].[NH2:28][C:29]1[N:34]=[CH:33][N:32]=[C:31]([CH2:35][OH:36])[CH:30]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.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]>[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[CH:13]=[C:12]([Cl:14])[C:11]([C:15]2[S:16][C:17]3[C:18]([NH:28][C:29]4[CH:30]=[C:31]([CH2:35][OH:36])[N:32]=[CH:33][N:34]=4)=[N:19][CH:20]=[C:21]([F:24])[C:22]=3[N:23]=2)=[C:10]([Cl:26])[CH:9]=1)([CH3:2])([CH3:3])[CH3:4]

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 21934615(6-Aminopyrimidin-4-yl)methanolHCID 86669030[3,5-Dichloro-4-(4-chloro-7-fluorothiazolo[5,4-c]pyridin-2-yl)phenyl]-carbamic acid tert-butyl ester

Produkt 1

HCID 66801633{3,5-Dichloro-4-[7-fluoro-4-(6-hydroxymethylpyrimidin-4-ylamino)-thiazolo[5,4-c]pyridin-2-yl]phenyl}-carbamic acid tert-butyl esterAusbeute 58 %

Reagenzien, Katalysatoren, Lösungsmittel 2

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

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of [3,5-dichloro-4-(4-chloro-7-fluorothiazolo[5,4-c]pyridin-2-yl)phenyl]-carbamic acid tert-butyl ester (150 mg, 0.33 mmol) in dioxane (5 mL), was added (6-aminopyrimidin-4-yl)methanol (45 mg, 0.36 mmol), XantPhos (19.4 mg, 0.033 mmol) and Cs2CO3 (218.3 mg, 0.67 mmol). The resultant mixture was degassed with argon for 10 minutes before Pd2(dba)3 (57.7 mg, 0.063 mmol) was added and the reaction mixture was heated at 100° C. for 18 hours in a sealed vial. After cooling to room temperature, the reaction mixture was filtered through Celite® washing with EtOAc (5 mL). The resultant residue was purified by column chromatography on silica gel eluting with 0-80% EtOAc in cyclohexane to afford the title compound as a white foam (102 mg, 58%). LCMS (Method D): RT=3.35 min, m/z: 538 [M+H+].

Aufarbeitung

  1. additionwas added
  2. temperatureAfter cooling to room temperature
  3. filtrationthe reaction mixture was filtered through Celite®
  4. washwashing with EtOAc (5 mL)
  5. customThe resultant residue was purified by column chromatography on silica gel eluting with 0-80% EtOAc in cyclohexane

Quellen und Nachweise

ORD-Eintrag
ord-cf8eb076ab1c43d08bdc442bda6afb3e
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08697708B2

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