Reaktion #626526

Reaktionsgleichung

3-(di-tert-butylphosphonium)propane sulfonate

6′-bromo-4,4-difluoro-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine

6′-Bromo-4,4-difluoro-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine

5-chloropyridin-3-ylboronic acid

3-(di-tert-butylphosphonium)propane sulfonate

K2CO3

5-chloropyridin-3-ylboronic acid

→

title compound

Ausbeute 38.0%

6′-(5-Chloropyridin-3-yl)-4,4-difluoro-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine

Ausbeute 38.0%

Lösungsmittel

Water

2-methyl-tetrahydrofuran

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe vial was flushed with Ar (g)
2. 2
   Sonstigecapped
3. 3
   Temperaturwas heated to 90° C. for 1 h
4. 4
   Extraktionthe residue was extracted with EtOAc (×3)
5. 5
   TrocknenThe organic phases were dried with MgSO4
6. 6
   Einengenconcentrated
7. 7
   SonstigeThe crude product was purified on a silica gel column (4 g SiO2, 7 M NH3 in MeOH in DCM 1:9/DCM 0-100%)

Vorschrift

Sodium tetrachloropalladate(II) (7.70 mg, 0.03 mmol), 3-(di-tert-butylphosphonium)propane sulfonate (7.02 mg, 0.03 mmol), 6′-bromo-4,4-difluoro-5″-methyl-3′H-dispiro[cyclohexane-1,2′-indene-1′,2″-imidazol]-4″-amine (Example 27, 100 mg, 0.26 mmol) and 5-chloropyridin-3-ylboronic acid (52.0 mg, 0.31 mmol) were added to a microwave vial and dissolved in 2-methyl-tetrahydrofuran (1 mL). K2CO3 (2M aq) (0.392 mL, 0.78 mmol) was added and the vial was flushed with Ar (g) and capped. The mixture was heated in a microwave reactor at 100° C. for 45 min. Additional sodium tetrachloropalladate(II) (7.70 mg, 0.03 mmol), 3-(di-tert-butylphosphonium)propane sulfonate (7.02 mg, 0.03 mmol) and 0.5 equiv. 5-chloropyridin-3-ylboronic acid was added to the reaction mixture and it was heated to 90° C. for 1 h. Water was added and the residue was extracted with EtOAc (×3). The organic phases were dried with MgSO4 and concentrated. The crude product was purified on a silica gel column (4 g SiO2, 7 M NH3 in MeOH in DCM 1:9/DCM 0-100%) to give the title compound (41 mg, 38% yield). 1H NMR (500 MHz, DMSO-d6) δ ppm 1.23-1.32 (m, 1 H), 1.52 (br. s., 2 H), 1.72 (br. s., 1 H), 1.79-1.98 (m, 4 H), 2.19 (s, 3 H), 3.08 (d, 1 H), 3.16 (d, 1 H), 6.62 (br. s., 2 H), 6.90 (d, 1 H), 7.43 (d, 1 H), 7.60 (dd, 1 H), 8.10 (t, 1 H), 8.57 (d, 1 H), 8.72 (d, 1 H). MS (APCI+) m/z 415.2 [M+H]+.

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