تفاعل #70729

معادلة التفاعل

sPhos

methyl 2-bromo-6-chloro-1-isopropyl-3-methyl-1H-indole-4-carboxylate

potassium ((dimethylamino)methyl)trifluoroborate

Potassium phosphate

→

methyl 6-chloro-2-((dimethylamino)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxylate

المردود 48.1%

المذيبات

EtOAc

water

water

dioxane

ظروف التفاعل

المعالجة

1. 1
   ترشيحfiltered
2. 2
   أخرىto remove insolubles
3. 3
   أخرىThe EtOAc phase was removed
4. 4
   تجفيفdried (Na2SO4)
5. 5
   ترشيحfiltered
6. 6
   تركيزconcentrated under vacuum
7. 7
   أخرىThe crude was purified by silica gel chromatography (Analogix
8. 8
   أخرىevaporated to dryness under vacuum

الإجراء التجريبي

To a stirred mixture of methyl 2-bromo-6-chloro-1-isopropyl-3-methyl-1H-indole-4-carboxylate (1.0 g, 2.90 mmol), potassium ((dimethylamino)methyl)trifluoroborate (0.5 g, 3.03 mmol) and Potassium phosphate (1.9 g, 8.95 mmol) (purged with N2)) in dioxane (3 mL) and water (3 mL) was added palladium(II) acetate (25 mg, 0.111 mmol) and sPhos (90 mg, 0.219 mmol). The reaction was heated to 100° C. and stirred for 18 hr under N2. LCMS showed that the reaction was complete. The reaction was diluted with EtOAc and water, and filtered to remove insolubles. The EtOAc phase was removed, dried (Na2SO4), filtered, and concentrated under vacuum. The crude was purified by silica gel chromatography (Analogix, SF25-40 g, 0 to 2% (5% NH4OH/MeOH) in CH2Cl2). The product fractions were combined, evaporated to dryness under vacuum to give the product methyl 6-chloro-2-((dimethylamino)methyl)-1-isopropyl-3-methyl-1H-indole-4-carboxylate (0.45 g, 1.394 mmol, 48.0% yield) as a light yellow oil (Only 84% pure by LCMS). This was used as is in the next reaction. 1H NMR (400 MHz, DMSO-d6) δ=7.82 (d, J=1.8 Hz, 1H), 7.28 (d, J=1.8 Hz, 1H), 4.96 (dt, J=7.1, 14.1 Hz, 1H), 3.88 (s, 3H), 3.52 (s, 2H), 2.17 (s, 3H), 2.16 (s, 6H), 1.53 (d, J=7.1 Hz, 6H). MS (ES)+m/e 323.2 [M+H]+, 278.1 [M+H]+ −45 (HNMe2).

المصدر