Azobisisobutyronitrile → HCID 22566242, compound

HRID 25172Notes

Reaction equation

HRID 25172 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([N:10]2[C:14]3[C:15](=[O:28])[N:16]([C:20]4[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=4[F:27])[CH2:17][CH2:18][CH2:19][C:13]=3[C:12]([C:29]([F:32])([F:31])[F:30])=[N:11]2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2].BrN1C(=O)CCC1=O.CC(N=NC(C#N)(C)C)(C#N)C>C(Cl)(Cl)(Cl)Cl>[C:1]([C:3]1[CH:4]=[C:5]([N:10]2[C:14]3[C:15](=[O:28])[N:16]([C:20]4[CH:25]=[CH:24][C:23]([I:26])=[CH:22][C:21]=4[F:27])[CH2:17][CH:18]=[CH:19][C:13]=3[C:12]([C:29]([F:31])([F:30])[F:32])=[N:11]2)[CH:6]=[CH:7][C:8]=1[F:9])#[N:2]

Participants

5

Reactant 3

HCID 6547AzobisisobutyronitrileHCID 67184N-bromobutanimideHCID 22566252HCID 22566252, compound

Product 1

HCID 22566242HCID 22566242, compound

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent

Procedure

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).

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered through Celite
  3. concentrationThe filtrate was concentrated to a brown solid
  4. dissolutionIt was then dissolved in 20 mL of THF
  5. addition1, 8-diazabicyclo[5, 4, 0]unden-7-ene (DBU, 0.14 mL) was added
  6. temperatureThe mixture was refluxed for 12 h
  7. customThe solvent was removed
  8. dissolutionIt was dissolved in EtOAc
  9. washwashed with water and brine
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-14f364a87736447cb65b6e943eeb2457
Source dataset
uspto-grants-2005_02
Patent number
US06858616B2

Reaction notes

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