Dimethylformamide → 5-[10-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazol-1-yl]-4-methylpyridine-2-carbonitrile

HRID 1628645Notes

Reaction equation

HRID 1628645 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[C:11]([CH3:13])[C:10]([N:14]2[C:20]3=[N:21][C:22]4[C:27]([Cl:28])=[CH:26][CH:25]=[C:24]([CH:29]([CH2:32][CH3:33])[CH2:30][CH3:31])[C:23]=4[N:19]3[CH2:18][CH2:17][CH2:16][CH2:15]2)=[CH:9][N:8]=1)(=O)=O.[CH3:36][N:37](C)C=O>C(OCC)(=O)C.[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:28][C:27]1[C:22]2[N:21]=[C:20]3[N:14]([C:10]4[C:11]([CH3:13])=[CH:12][C:7]([C:36]#[N:37])=[N:8][CH:9]=4)[CH2:15][CH2:16][CH2:17][CH2:18][N:19]3[C:23]=2[C:24]([CH:29]([CH2:32][CH3:33])[CH2:30][CH3:31])=[CH:25][CH:26]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 57786014HCID 57786014, compound

Product 1

HCID 577859415-[10-Chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazol-1-yl]-4-methylpyridine-2-carbonitrileYield 76%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Under argon atmosphere a mixture of 5-[10-chloro-7-(1-ethylpropyl)-2,3,4,5-tetrahydro-1H-[1,3]diazepino[1,2-a]benzimidazol-1-yl]-4-methylpyridin-2-yl trifluoromethanesulfonate (Example 58; 285 mg, 0.537 mmol), zinc cyanide (94.5 mg, 0.805 mmol), tetrakis(triphenylphosphine)palladium(0) (62.1 mg, 0.0537 mmol) and N,N-dimethylformamide (2.7 mL) was stirred at 120° C. for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a 10-40% ethyl acetate/n-hexane gradient mixture to give the title compound as a solid (166 mg, 0.407 mmol, 76%). Analytically pure material was obtained by recrystallization from ethyl acetate/n-hexane.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography on silica gel eluting with a 10-40% ethyl acetate/n-hexane gradient mixture

Sources & evidence

ORD record
ord-ac5aecb69f2c401e88ce4f3332de4cea
Source dataset
uspto-grants-2014_07
Patent number
US08785460B2

Reaction notes

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