Lithium Chloride → [4-(7-Chloro-imidazo[1,2-a]pyridin-3-yl)-thiazol-2-ylmethyl]-carbamic acid tert-butyl ester

HRID 1446676

Reaktionsgleichung

Reaktionsgleichung von HRID 1446676
[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]1[S:10][CH:11]=[C:12]([Sn](C)(C)C)[N:13]=1)([CH3:4])([CH3:3])[CH3:2].[Cl:19][C:20]1[CH:25]=[CH:24][N:23]2[C:26](I)=[CH:27][N:28]=[C:22]2[CH:21]=1.[Li+].[Cl-]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([O:5][C:6](=[O:18])[NH:7][CH2:8][C:9]1[S:10][CH:11]=[C:12]([C:26]2[N:23]3[CH:24]=[CH:25][C:20]([Cl:19])=[CH:21][C:22]3=[N:28][CH:27]=2)[N:13]=1)([CH3:4])([CH3:3])[CH3:2]

Komponenten

6

Edukt 3

HCID 433294Lithium ChlorideHCID 574976977-Chloro-3-iodoimidazo[1,2-a]pyridineHCID 66623970(4-Trimethylstannyl-thiazol-2-ylmethyl)-carbamic acid tert-butyl ester

Produkt 1

HCID 68545966[4-(7-Chloro-imidazo[1,2-a]pyridin-3-yl)-thiazol-2-ylmethyl]-carbamic acid tert-butyl esterAusbeute 38,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

To a solution of (4-trimethylstannyl-thiazol-2-ylmethyl)-carbamic acid tert-butyl ester (0.480 g, 1.27 mmol, 1.0 eq.) [prepared as in the PCT application WO2004046101, Jun. 3, 2004, filed Nov. 10, 2003] in anhydrous dioxane (4 mL), add 7-chloro-3-iodo-imidazo[1,2-a]pyridine (0.354 g, 1.27 mmol, 1.0 eq.) and LiCl (0.162 g, 3.0 eq.). Add Pd(PPh3)4 (0.102 g, 0.07 eq.). Deoxygenate the reaction mixture and fill with nitrogen. Stir at 90° C. over night, cool, then dilute with 5% MeOH/DCM (100 mL), wash with saturated aqueous saturated sodium chloride (2×20 mL), water (2×20 mL), dry, filter, and concentrate. Chromatograph on silica gel first with a 50%-100% EtOAc/DCM gradient then a 5% MeOH/DCM gradient to afford 0.180 g of the title compound, which is used in the next step without further purification: MS(ES), m/z 365 (M+1).

Aufarbeitung

  1. customDeoxygenate the reaction mixture and fill with nitrogen
  2. temperaturecool
  3. additiondilute with 5% MeOH/DCM (100 mL)
  4. washwash with saturated aqueous saturated sodium chloride (2×20 mL), water (2×20 mL)
  5. customdry
  6. filtrationfilter
  7. concentrationconcentrate

Quellen und Nachweise

ORD-Eintrag
ord-275102f6b24c4382811d7e18e5adea94
Quelldatensatz
uspto-grants-2010_02
Patentnummer
US07666879B2

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