Potassium Carbonate → Tert-butyl 4-[(2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl}-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylate

HRID 906428Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 906428
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]1([CH2:18][O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])[CH2:17][CH2:16][CH2:15]1)[CH:6]=[C:5]2[CH2:27][N:28]1[CH2:33][CH2:32][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:30][CH2:29]1.[CH:41]1([NH:44][C:45](=[O:63])[C:46]2[CH:51]=[C:50](B3OC(C)(C)C(C)(C)O3)[C:49]([CH3:61])=[C:48]([F:62])[CH:47]=2)[CH2:43][CH2:42]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Si:20]([O:19][CH2:18][C:14]1([CH2:13][N:7]2[CH:6]=[C:5]([CH2:27][N:28]3[CH2:29][CH2:30][N:31]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:32][CH2:33]3)[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([C:50]4[CH:51]=[C:46]([C:45](=[O:63])[NH:44][CH:41]5[CH2:42][CH2:43]5)[CH:47]=[C:48]([F:62])[C:49]=4[CH3:61])[CH:3]=3)[C:8]2=[O:12])[CH2:17][CH2:16][CH2:15]1)([C:23]([CH3:24])([CH3:26])[CH3:25])([CH3:22])[CH3:21]

Komponenten

5

Edukt 3

HCID 11430Potassium CarbonateHCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 67390960tert-Butyl 4-[(6-bromo-2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl}-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylate

Produkt 1

HCID 67391526Tert-butyl 4-[(2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl}-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylateAusbeute 55 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

A solution of tert-butyl 4-[(6-bromo-2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl}-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylate (Example 27c, 0.153 g) in DMF (4 mL) was treated with N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.077 g), Pd-118 (4.71 mg) and potassium carbonate (0.067 g) under nitrogen. The resulting mixture was stirred at 75° C. for 8 h. The reaction was partitioned between ethyl acetate and water. The aqueous was extracted with ethyl acetate (2×100 mL) before washing the organics with water (3×100 mL) and brine (3×100 mL). The organic was dried (MgSO4), filtered, and evaporated under reduced pressure to afford the crude product. The crude product was purified (SiO2 chromatography, elution with 30% ethyl acetate/isohexane) to afford the subtitle compound (0.099 g) as an oil.

Aufarbeitung

  1. customThe reaction was partitioned between ethyl acetate and water
  2. extractionThe aqueous was extracted with ethyl acetate (2×100 mL)
  3. washbefore washing the organics with water (3×100 mL) and brine (3×100 mL)
  4. dry with materialThe organic was dried (MgSO4)
  5. filtrationfiltered
  6. customevaporated under reduced pressure
  7. customto afford the crude product
  8. customThe crude product was purified
  9. wash(SiO2 chromatography, elution with 30% ethyl acetate/isohexane)

Quellen und Nachweise

ORD-Eintrag
ord-d03f84d99cd84cb2a9203627f8c1442b
Quelldatensatz
uspto-grants-2011_09
Patentnummer
US08012980B2

Notizen zur Reaktion

Wird geladen…