Methane → HCID 68670057, compound

HRID 2047407Notes

Reaction equation

HRID 2047407 reaction equation
C[Al](C)C.[C:5]1([NH2:12])[C:6]([NH2:11])=[CH:7][CH:8]=[CH:9][CH:10]=1.C.C(OC([N:21]1[CH2:27][CH2:26][CH2:25][N:24]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([C:35](OCC)=O)[CH:29]=2)[CH2:23][CH2:22]1)=O)(C)(C)C>C1(C)C=CC=CC=1.CO.O>[Cl:34][C:31]1[CH:32]=[CH:33][C:28]([N:24]2[CH2:25][CH2:26][CH2:27][NH:21][CH2:22][CH2:23]2)=[CH:29][C:30]=1[C:35]1[NH:12][C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[N:11]=1

Participants

8

Reactant 4

HCID 297MethaneHCID 7243O-PhenylenediamineHCID 16682925TrimethylaluminumHCID 68670654HCID 68670654, compound

Product 1

HCID 68670057HCID 68670057, compoundYield 71.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of trimethylaluminium (2.0 M solution in toluene) (90 mL, 180 mmol) in toluene (300 mL) cooled to 0° C. under nitrogen was added benzene-1,2-diamine (6.5 g, 60 mmol) portionwise. The solution was stirred for 30 minutes at 0° C. then at 15-20° C. until evolution of methane ceased. 4-(4-chloro-3-ethoxycarbonyl-phenyl)-[1,4]diazepane-1-carboxylic acid tert-butyl ester (15.2 g, 40 mmol) was added in one portion to the resulting solution. The reaction was heated to reflux for 24 h then cooled to 0° C. Water (70 mL) was added carefully followed by MeOH (700 mL) The solid precipitated was filtered and the filtrate was concentrated under reduced pressure. The precipitate was washed with hot DCM:MeOH 1:1 (400 mL) followed by AcOEt (200 mL) The solution was concentrated under reduced pressure. Two extracts were combined and purified by flash chromatography (eluent: AcOEt:MeOH:NH3 gradient from 100% AcOEt to AcOEt:MeOH:NH3 73:25:2) to afford 9.3 g of a mixture of 2-(2-Chloro-5-[1,4]diazepan-1-yl-phenyl)-1H-benzoimidazole and N-(2-amino-phenyl)-2-chlorodiazepan-1-yl-benzamide.

Workup

  1. customat 15-20° C.
  2. temperatureThe reaction was heated
  3. temperatureto reflux for 24 h
  4. temperaturethen cooled to 0° C
  5. customprecipitated
  6. filtrationwas filtered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. washThe precipitate was washed with hot DCM:MeOH 1:1 (400 mL)
  9. concentrationwas concentrated under reduced pressure
  10. custompurified by flash chromatography (eluent: AcOEt:MeOH:NH3 gradient from 100% AcOEt to AcOEt:MeOH:NH3 73:25:2)

Sources & evidence

ORD record
ord-93ecb404173d46919ef85e228d996f4f
Source dataset
uspto-grants-2013_11
Patent number
US08592463B2

Reaction notes

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