Sodium Carbonate → HCID 178434248, Verbindung

Temperatur

150 °C

To a solution of 1.0 mL dioxane, 0.5 mL distilled water and sodium carbonate (35.0 mg, 0.33 mmol) in a 5 mL microwave tube, were added 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (32.0 mg, 0.124 mmol) and (S)-N-(5-bromothiazol-2-yl)-N-(2-(1,3-dioxoisoindolin-2-yl)-3-phenylpropyl)acetamide (40.0 mg, 0.0826 mmol). The reaction mixture was degassed by bubbling nitrogen into the microwave tube for 30 seconds. Subsequently, tetrakis(triphenylphosphine)palladium(0) (10.0 mg, 0.0083 mmol) was added to the tube, and the mixture was heated at 150° C. in a Smith microwave synthesizer. After heating for 25 minutes, the reaction mixture was filtered through a pad of Celite and washed with MeOH. The filtrate was evaporated off, and the resulting residue was diluted with 1.5 mL MeOH, 1.5 mL water, and 1.5 mL hydrazine. The resulting mixture was transferred to a 5 mL microwave tube and heated at 150° C. After heating for 33 minutes, silica gel (10.0 g) was added to the reaction mixture, and the mixture was concentrated to dryness. The resulting solid was directly loaded on a silica gel column and chromatography separation was performed with DCM:MeOH (97:3) as the eluant to afford the desired compound N-((S)-2-amino-3-phenylpropyl)-5-(3-methyl-1H-indazol-5-yl)thiazol-2-amine as a colorless solid (8.0 mg, 26.6%). HRMS Theoretical (M+H) 364.15904, found 364.15915.

1. customThe reaction mixture was degassed
2. customby bubbling nitrogen into the microwave tube for 30 seconds
3. temperatureAfter heating for 25 minutes
4. filtrationthe reaction mixture was filtered through a pad of Celite
5. washwashed with MeOH
6. customThe filtrate was evaporated off
7. additionthe resulting residue was diluted with 1.5 mL MeOH, 1.5 mL water, and 1.5 mL hydrazine
8. customThe resulting mixture was transferred to a 5 mL microwave tube
9. temperatureheated at 150° C
10. temperatureAfter heating for 33 minutes
11. additionsilica gel (10.0 g) was added to the reaction mixture
12. concentrationthe mixture was concentrated to dryness
13. customThe resulting solid was directly loaded on a silica gel column and chromatography separation

ORD-Eintrag

ord-a499be851528433f81f76f4a4c472ba3

Quelldatensatz

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07514566B2