Sodium Bicarbonate → Tert-butyl 1-(6-chloro-4-(2-(5-fluoro-2-(2-(2-oxoimidazolidin-1-yl)ethylamino)pyrimidin-4-yl)benzo[b]thiophen-7-yl)pyridin-3-yl)ethylcarbamate

HRID 561030Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 561030
[C:1]([O:5][C:6](=[O:18])[NH:7][CH:8]([C:10]1[CH:11]=[N:12][C:13]([Cl:17])=[CH:14][C:15]=1I)[CH3:9])([CH3:4])([CH3:3])[CH3:2].[F:19][C:20]1[C:21]([C:35]2[S:39][C:38]3[C:40](B4OC(C)(C)C(C)(C)O4)=[CH:41][CH:42]=[CH:43][C:37]=3[CH:36]=2)=[N:22][C:23]([NH:26][CH2:27][CH2:28][N:29]2[CH2:33][CH2:32][NH:31][C:30]2=[O:34])=[N:24][CH:25]=1.C([O-])(O)=O.[Na+]>C(#N)C.O.C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[Cl:17][C:13]1[N:12]=[CH:11][C:10]([CH:8]([NH:7][C:6](=[O:18])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH3:9])=[C:15]([C:40]2[C:38]3[S:39][C:35]([C:21]4[C:20]([F:19])=[CH:25][N:24]=[C:23]([NH:26][CH2:27][CH2:28][N:29]5[CH2:33][CH2:32][NH:31][C:30]5=[O:34])[N:22]=4)=[CH:36][C:37]=3[CH:43]=[CH:42][CH:41]=2)[CH:14]=1

Komponenten

8

Edukt 3

HCID 516892Sodium BicarbonateHCID 666734811-(2-{5-Fluoro-4-[7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[b]thiophen-2-yl]-pyrimidin-2-ylamino}-ethyl)-imidazolidin-2-oneHCID 86640498[1-(6-Chloro-4-iodo-pyridin-3-yl)-ethyl]-carbamic acid tert-butyl ester

Produkt 1

HCID 86640497Tert-butyl 1-(6-chloro-4-(2-(5-fluoro-2-(2-(2-oxoimidazolidin-1-yl)ethylamino)pyrimidin-4-yl)benzo[b]thiophen-7-yl)pyridin-3-yl)ethylcarbamateAusbeute 55,3 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 24290Palladium ChlorideKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

In a microwave vial, combine [1-(6-chloro-4-iodo-pyridin-3-yl)-ethyl]-carbamic acid tert-butyl ester (250 mg, 0.65 mmol) and 1-(2-{5-fluoro-4-[7-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzo[b]thiophen-2-yl]-pyrimidin-2-ylamino}-ethyl)-imidazolidin-2-one (380 mg, 0.78 mmol), bis(diphenylphosphino)ferrocene)dichloro palladium (53 mg, 0.07 mmol) and NaHCO3 (110 mg, 1.31 mmol) in acetonitrile (7 mL) and water (3 mL). Purge the mixture with nitrogen for 5 min. Heat the mixture at 100° C. for 15 min in a microwave. Remove solvent on a rotovap. Purify by normal phase column chromatography using 0.5% to 5% MeOH in dichloromethane to get off white solid product (220 mg). MS (ES) m/z 612 [M+1]+

Aufarbeitung

  1. customPurge the mixture with nitrogen for 5 min
  2. customPurify by normal phase column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-3b623e63df59401cb1486053ee6778e2
Quelldatensatz
uspto-grants-2011_11
Patentnummer
US08063212B2

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