Triethylamine → 1-oxo-N-[3-(1-trityl-1H-imidazol-4-yl)phenyl]-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]benzimidazole-8-carboxamide

HRID 1521759Notes

Reaction equation

HRID 1521759 reaction equation
[O:1]=[C:2]1[C:8]2=[N:9][C:10]3[CH:15]=[CH:14][C:13]([C:16]([OH:18])=O)=[CH:12][C:11]=3[N:7]2[CH2:6][CH2:5][CH2:4][NH:3]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[C:41]([N:60]1[CH:64]=[C:63]([C:65]2[CH:66]=[C:67]([CH:69]=[CH:70][CH:71]=2)[NH2:68])[N:62]=[CH:61]1)([C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C(N(CC)CC)C>CN(C=O)C.CN(C1C=CN=CC=1)C.O>[O:1]=[C:2]1[C:8]2=[N:9][C:10]3[CH:15]=[CH:14][C:13]([C:16]([NH:68][C:67]4[CH:69]=[CH:70][CH:71]=[C:65]([C:63]5[N:62]=[CH:61][N:60]([C:41]([C:54]6[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=6)([C:48]6[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=6)[C:42]6[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=6)[CH:64]=5)[CH:66]=4)=[O:18])=[CH:12][C:11]=3[N:7]2[CH2:6][CH2:5][CH2:4][NH:3]1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 114751133-(1-trityl-1H-imidazol-4-yl)aniline2×HCID 672364761-Oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]benzimidazole-8-carboxylic acid2×

Product 1

HCID 672378591-oxo-N-[3-(1-trityl-1H-imidazol-4-yl)phenyl]-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]benzimidazole-8-carboxamideYield 73%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A solution of 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]benzimidazole-8-carboxylic acid (Intermediate B, 59 mg, 0.15 mmol) and TBTU (52 mg, 0.16 mmol) in DMF (2 mL) is stirred for 20 min at room temperature. 3-(1-Tritylimidazol-4-yl)-aniline (Intermediate O, 36 mg, 0.15 mmol) and triethylamine (15 mg, 0.15 mmol) are added and the solution stirred at room temperature for 4 h. DMAP (5 mg, 0.04 mmol) is added and the solution is heated at 60° C. overnight. The reaction is cooled to room temperature and H2O was added. The resulting precipitate is filtered off and purified via flash column chromatography using a gradient elution of 0-10% CH2Cl2/methanol, containing 1% NH4OH to afford the title compound as an oil (67 mg, 73%).

Workup

  1. temperaturethe solution is heated at 60° C. overnight
  2. temperatureThe reaction is cooled to room temperature
  3. filtrationThe resulting precipitate is filtered off
  4. custompurified via flash column chromatography
  5. washa gradient elution of 0-10% CH2Cl2/methanol
  6. additioncontaining 1% NH4OH

Sources & evidence

ORD record
ord-b358dfcec2f949ccb382429b044c5157
Source dataset
uspto-grants-2015_07
Patent number
US09073926B2

Reaction notes

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