Dimethylformamide → HCID 87869912, compound

HRID 507082Notes

Reaction equation

HRID 507082 reaction equation
[H-].[Na+].[F:3][C:4]([F:40])([F:39])[C:5]1[CH:6]=[C:7]([CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1)[CH2:8][NH:9][CH:10]1[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][CH:20]([CH3:22])[CH3:21])=[O:18])[C:12]2[C:23]([CH3:31])=[C:24]([C:27]([F:30])([F:29])[F:28])[CH:25]=[CH:26][C:11]1=2.[CH3:41][N:42](C)C=O.N#CBr>CS(C)=O.C(OCC)(=O)C.O>[F:40][C:4]([F:3])([F:39])[C:5]1[CH:6]=[C:7]([CH:32]=[C:33]([C:35]([F:36])([F:38])[F:37])[CH:34]=1)[CH2:8][N:9]([C:41]#[N:42])[CH:10]1[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][CH:20]([CH3:21])[CH3:22])=[O:18])[C:12]2[C:23]([CH3:31])=[C:24]([C:27]([F:28])([F:29])[F:30])[CH:25]=[CH:26][C:11]1=2

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 10476Cyanogen Bromide3×HCID 24758Sodium hydride3×HCID 87393980HCID 87393980, compound

Product 1

HCID 87869912HCID 87869912, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of sodium hydride 60% in mineral oil (32 mg, 0.81 mmol) in dry dimethyl sulfoxide (3 mL), add isopropyl 5-(3,5-bistrifluoromethyl-benzylamino)-9-methyl-8-trifluormethyl-2,3,4,5-tetrahydrobenzo[b]azepine-1-carboxylate (300 mg, 0.54 mmol) and dry dimethylformamide (2 mL). Add cyanogen bromide (176 mg, 1.62 mmol) and stir the reaction mixture at room temperature overnight. Add sodium hydride 60% in mineral oil (32 mg, 0.81 mmol) and cyanogen bromide (176 mg, 1.62 mmol) and stir at room temperature for one hour. Add additional sodium hydride 60% in mineral oil (32 mg, 0.81 mmol) and cyanogen bromide (176 mg, 1.62 mmol) and stir one hour. Add water and ethyl acetate. Separate the layers and dry the organic phase over anhydrous magnesium sulfate, filter and remove the solvent under reduced pressure. Purify the residue by flash chromatography, eluting with hexanes/ethyl acetate, to afford the titled compound (124 mg, 40%). MS (ES+): 582 (M+H).

Workup

  1. customSeparate the layers
  2. dry with materialdry the organic phase over anhydrous magnesium sulfate
  3. filtrationfilter
  4. customremove the solvent under reduced pressure
  5. customPurify the residue by flash chromatography
  6. washeluting with hexanes/ethyl acetate

Sources & evidence

ORD record
ord-893a0a9ccdc34ed58348fc9aa07c6feb
Source dataset
uspto-grants-2010_08
Patent number
US07786108B2

Reaction notes

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