تفاعل #1278267

معادلة التفاعل

6-bromo-3-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridine

DMF

→

desired intermediate

المردود 38.0%

5-(2-Cyclopropylmethylamino-thiazol-4-yl)-pyridine-2-carbonitrile

المردود 38.0%

المذيبات

EtOAc

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةCool the mixture to room temperature
2. 2
   غسيلwash with 5% aqueous sodium chloride (3×30 mL)
3. 3
   أخرىCollect the organic layer
4. 4
   تركيزconcentrate in vacuo
5. 5
   أخرىPurify the residue by chromatography on silica gel (40 g)
6. 6
   غسيلeluting with hexane/(THF with 1% methanol) (4:1)

الإجراء التجريبي

Slurry 6-bromo-3-(2-cyclopropylmethylamino-thiazol-4-yl)-pyridine (1.1 g, 3.6 mmol), 1,1′-bis-(diphenylphosphino)ferrocene (320 mg, 0.6 mmol), zinc cyanide (337 mg, 2.9 mmol) and tris(dibenzylideneacetone)dipalladium(0) (231 mg, 0.25 mmol) in wet DMF (6 mL). Stir the mixture in a sealed tube at 115° C. for 6 h. Cool the mixture to room temperature, dilute with EtOAc (50 mL) and wash with 5% aqueous sodium chloride (3×30 mL). Collect the organic layer and concentrate in vacuo. Purify the residue by chromatography on silica gel (40 g) eluting with hexane/(THF with 1% methanol) (4:1) to obtain the desired intermediate (350 mg, 38%). MS (ES+) m/z: 257.3 (M+H)+.

المصدر