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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 1399001
Notes
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Reaction equation

HRID 1399001 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
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 577860145-[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

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 11186
Zinc cyanide (Zn(CN)2)
Catalyst
HCID 178418397HCID 178418397, compoundCatalyst
HCID 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-d767c3628e84410fbfc401c8b248de37
Source dataset
uspto-grants-2014_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08901141B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes