Lithium Chloride → (S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(5-methyl-6-(1-methyl-1H-indazol-5-yl)pyridin-2-yl)benzo[d]thiazol-6-yl)acetate

HRID 879561Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 879561
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]3[C:14](=[CH:15][CH:16]=2)[N:13]([CH3:17])[N:12]=[CH:11]3)[C:5]([CH3:18])=[CH:4][CH:3]=1.[Li+].[Cl-].Br[C:22]1[S:23][C:24]2[C:30]([C:31]3[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=3)=[C:29]([C@H:38]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])[C:39]([O:41][CH2:42][CH3:43])=[O:40])[C:28]([CH3:49])=[CH:27][C:25]=2[N:26]=1>O1CCOCC1.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.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:45]([O:44][C@@H:38]([C:29]1[C:28]([CH3:49])=[CH:27][C:25]2[N:26]=[C:22]([C:2]3[CH:3]=[CH:4][C:5]([CH3:18])=[C:6]([C:8]4[CH:9]=[C:10]5[C:14](=[CH:15][CH:16]=4)[N:13]([CH3:17])[N:12]=[CH:11]5)[N:7]=3)[S:23][C:24]=2[C:30]=1[C:31]1[CH:32]=[CH:33][C:34]([Cl:37])=[CH:35][CH:36]=1)[C:39]([O:41][CH2:42][CH3:43])=[O:40])([CH3:46])([CH3:47])[CH3:48]

Komponenten

8

Edukt 3

HCID 433294Lithium ChlorideHCID 86700141(S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetateHCID 867003845-(6-chloro-3-methylpyridin-2-yl)-1-methyl-1H-indazole

Produkt 1

HCID 86700385(S)-ethyl 2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methyl-2-(5-methyl-6-(1-methyl-1H-indazol-5-yl)pyridin-2-yl)benzo[d]thiazol-6-yl)acetate

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 178418476HCID 178418476, VerbindungKatalysatorHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

In a 10 mL reaction vial, 5-(6-chloro-3-methylpyridin-2-yl)-1-methyl-1H-indazole (100 mg, 0.389 mmol) was dissolved in dioxane (5 mL) at rt. The solution was bubbled with argon for 5 min. Then Sn2(n-Bu)6 (0.253 mL, 0.508 mmol), LiCl (100 mg, 2.38 mmol), Pd(PPh3)2Cl2 (27 mg, 0.039 mmol) and Pd(PPh3)4 (45 mg, 0.039 mmol) were added sequentially. The resulting reaction mixture was sealed and heated to 90° C. in oil bath. To this mixture, a solution of (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (289 mg, 0.583 mmol) in dioxane (5 mL) was added slowly through syringe pump over 1.5 h. The resulting reaction mixture was stirred at 100° C. in oil bath for 16 h. The reaction was then diluted with EtOAc (20 mL) and filtered to remove solid. The filtrate was concentrated and purified on silica gel column with 0-20% EtOAc/Hex to afford product as. LCMS-ESI+: calc'd for: C36H35ClN4O3S: 639.2, 640.2, 641.2 (M+H+); found: 639.1, 640.1, 641.1 (M+H+).

Aufarbeitung

  1. customIn a 10 mL reaction vial
  2. customThe solution was bubbled with argon for 5 min
  3. customThe resulting reaction mixture
  4. customwas sealed
  5. customThe resulting reaction mixture
  6. filtrationfiltered
  7. customto remove solid
  8. concentrationThe filtrate was concentrated
  9. custompurified on silica gel column with 0-20% EtOAc/Hex
  10. customto afford product as

Quellen und Nachweise

ORD-Eintrag
ord-2023eaffc3b74d988eb1a387fd66f69f
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08987250B2

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