N-methyl-2-pyrrolidone → 11-[6-(hydroxymethyl)-3-azabicyclo[4.1.0]hept-3-yl]-2,3-dihydro-1H-cyclopenta[4,5]pyrido[1,2-a]benzimidazole-4-carboxamide

HRID 70796Notes

Reaction equation

HRID 70796 reaction equation
Cl[C:2]1[N:10]2[C:6](=[N:7][C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=32)[C:5]([C:15]([NH2:17])=[O:16])=[C:4]2[CH2:18][CH2:19][CH2:20][C:3]=12.CCN(C(C)C)C(C)C.CN1C(=O)CCC1.Cl.[CH:38]12[CH2:44][C:43]1([CH2:45][OH:46])[CH2:42][CH2:41][NH:40][CH2:39]2>O>[OH:46][CH2:45][C:43]12[CH2:44][CH:38]1[CH2:39][N:40]([C:2]1[N:10]3[C:6](=[N:7][C:8]4[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=43)[C:5]([C:15]([NH2:17])=[O:16])=[C:4]3[CH2:18][CH2:19][CH2:20][C:3]=13)[CH2:41][CH2:42]2

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 86677058HCID 86677058, compoundHCID 867626763-Azabicyclo[4.1.0]heptan-6-ylmethanol;hydrochloride

Product 1

HCID 7126859411-[6-(hydroxymethyl)-3-azabicyclo[4.1.0]hept-3-yl]-2,3-dihydro-1H-cyclopenta[4,5]pyrido[1,2-a]benzimidazole-4-carboxamideYield 74.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

11-chloro-2,3-dihydro-1H-cyclopenta[4,5]pyrido[1,2-a]benzimidazole-4-carboxamide (800 mg) and DIPEA (1.95 ml) were added to an NMP suspension of 3-azabicyclo[4.1.0]hept-6-ylmethanol hydrochloride (1.01 g), and stirring was performed at 220° C. for 60 minutes under microwave irradiation. The reaction liquid was added to water and the precipitate was collected by filtration. The resulting solid was purified by silica gel column chromatography (MeOH/chloroform) to obtain 11-[6-(hydroxymethyl)-3-azabicyclo[4.1.0]hept-3-yl]-2,3-dihydro-1H-cyclopenta[4,5]pyrido[1,2-a]benzimidazole-4-carboxamide (788 mg).

Workup

  1. customwas performed at 220° C. for 60 minutes under microwave irradiation
  2. customThe reaction liquid
  3. filtrationthe precipitate was collected by filtration
  4. customThe resulting solid was purified by silica gel column chromatography (MeOH/chloroform)

Sources & evidence

ORD record
ord-2d3ceea441bf4ee392c878062fd6aba4
Source dataset
uspto-grants-2014_09
Patent number
US08822688B2

Reaction notes

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