تفاعل #53450

معادلة التفاعل

AIBN

1-(3-Cyano-4-fluorophenyl)-3-trifluoromethyl-7-(2-fluoro-4-iodophenyl)-4,5,6,7-tetrahydropyrazolo-[3,4-c]azepin-8-one

N-bromosuccinimide

→

1-(3-Cyano-4-fluorophenyl)-3-trifluoromethyl-7-(2-fluoro-4-iodophenyl)-6,7-dihydropyrazolo-[3,4-c]azepin-8-one

المذيبات

CCl4

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةThe reaction mixture was cooled
2. 2
   ترشيحfiltered through Celite
3. 3
   تركيزThe filtrate was concentrated to a brown solid
4. 4
   workup.DISSOLUTIONIt was then dissolved in 20 mL of THF
5. 5
   workup.ADDITION1, 8-diazabicyclo[5, 4, 0]unden-7-ene (DBU, 0.14 mL) was added
6. 6
   درجة الحرارةThe mixture was refluxed for 12 h
7. 7
   أخرىThe solvent was removed
8. 8
   workup.DISSOLUTIONIt was dissolved in EtOAc
9. 9
   غسيلwashed with water and brine
10. 10
    تجفيفdried over MgSO4
11. 11
    تركيزconcentrated

الإجراء التجريبي

1-(3-Cyano-4-fluorophenyl)-3-trifluoromethyl-7-(2-fluoro-4-iodophenyl)-4,5,6,7-tetrahydropyrazolo-[3,4-c]azepin-8-one prepared by the same methods as shown in Example 40 (0.50 g, 0.90 mmol), N-bromosuccinimide (0.19 g, 1.08 mmol), and AIBN (9.0 mg) were refluxed with 50 mL of CCl4 under N2 for 2 h. The reaction mixture was cooled and filtered through Celite. The filtrate was concentrated to a brown solid. It was then dissolved in 20 mL of THF and 1, 8-diazabicyclo[5, 4, 0]unden-7-ene (DBU, 0.14 mL) was added. The mixture was refluxed for 12 h. The solvent was removed. It was dissolved in EtOAc and washed with water and brine, dried over MgSO4 and concentrated. Flash chromatography on silica gel with 15% EtOAc in hexane gave 0.21 g of 1-(3-Cyano-4-fluorophenyl)-3-trifluoromethyl-7-(2-fluoro-4-iodophenyl)-6,7-dihydropyrazolo-[3,4-c]azepin-8-one. The title compound was then prepared from 1-(3-Cyano-4-fluorophenyl)-3-trifluoromethyl-7-(2-fluoro-4-iodophenyl)-6,7-dihydropyrazolo-[3,4-c]azepin-8-one by the same methods shown in Example 40. LRMS (ES+): 603.2, (M+H)+. 1H NMR (CDCl3) 7.82 (d, 1H), 7.73 (m, 2H), 7.54-7.35 (m, 4H), 7.09 (dd, 4H), 6.46 (m, 1H), 4.34 (s, 2H), 4.32 (d, 2H), 3.86 (bs, 2H), 3.59 (m, 2H), 2.58 (m, 2H), 2.01 (m, 2H), 1.85 (m, 2H).

المصدر