Dichloromethane → Methyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-chloropyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanecarboxylate

HRID 2047233Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2047233
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](B2OC(C)(C)C(C)(C)O2)=[CH:4][N:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl.[CH3:28][O:29][C:30]([CH:32]1[CH2:37][CH2:36][CH:35]([C:38]2[CH:43]=[C:42]([N:44]([CH2:53][O:54][CH2:55][CH2:56][Si:57]([CH3:60])([CH3:59])[CH3:58])[CH2:45][O:46][CH2:47][CH2:48][Si:49]([CH3:52])([CH3:51])[CH3:50])[N:41]3[N:61]=[CH:62][C:63](I)=[C:40]3[N:39]=2)[CH2:34][CH2:33]1)=[O:31]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:51][Si:49]([CH3:50])([CH3:52])[CH2:48][CH2:47][O:46][CH2:45][N:44]([CH2:53][O:54][CH2:55][CH2:56][Si:57]([CH3:60])([CH3:59])[CH3:58])[C:42]1[N:41]2[N:61]=[CH:62][C:63]([C:5]3[CH:4]=[N:3][C:2]([Cl:1])=[CH:7][CH:6]=3)=[C:40]2[N:39]=[C:38]([CH:35]2[CH2:36][CH2:37][CH:32]([C:30]([O:29][CH3:28])=[O:31])[CH2:33][CH2:34]2)[CH:43]=1

Komponenten

7

Edukt 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 27947192-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 667384164-{7-[Bis-(2-trimethylsilanyl-ethoxymethyl)-amino]-3-iodo-pyrazolo[1,5-a]pyrimidin-5-yl}-cyclohexanecarboxylic acid methyl ester

Produkt 1

HCID 86664799Methyl 4-(7-(bis((2-(trimethylsilyl)ethoxy)methyl)amino)-3-(6-chloropyridin-3-yl)pyrazolo[1,5-a]pyrimidin-5-yl)cyclohexanecarboxylateAusbeute 75,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)KatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

2-Chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.55 mmol, 131 mg), K3PO4 (1.36 mmol, 290 mg), and PdCl2(dppf).CH2Cl2 (0.045 mmol, 37 mg) is added to a solution of 4-{7-[Bis-(2-trimethylsilanyl-ethoxymethyl)-amino]-3-iodo-pyrazolo[1,5-a]pyrimidin-5-yl}-cyclohexanecarboxylic acid methyl ester (0.45 mmol, 300 mg) in dioxane (3.8 mL). To this suspension is added distilled H2O (0.38 mL). The resulting solution is stirred at 90° C. under argon for 18 hours. The reaction mixture is concentrated in vacuo and then purified via silica gel chromatography (0% to 60% ethyl acetate in hexanes gradient) to yield the title compound (220 mg, 75% yield) as yellow oil. LC-MS: 646 [M+H].

Aufarbeitung

  1. additionTo this suspension is added
  2. distillationdistilled H2O (0.38 mL)
  3. concentrationThe reaction mixture is concentrated in vacuo
  4. custompurified via silica gel chromatography (0% to 60% ethyl acetate in hexanes gradient)

Quellen und Nachweise

ORD-Eintrag
ord-1af29f7a3b40424db9fc63af006893d6
Quelldatensatz
uspto-grants-2013_11
Patentnummer
US08591943B2

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