Pyridine → Ammonia methanol

HRID 1584433Notes

Reaction equation

HRID 1584433 reaction equation
Cl[C:2]1[N:6]([CH2:7][C:8]2[O:9][C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:11][CH:12]=2)[C:5]2[CH:18]=[CH:19][CH:20]=[CH:21][C:4]=2[N:3]=1.[NH:22]1[CH2:28][CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.N12CCCN=C1CCCCC2.N1C=CC=CC=1>CO>[NH3:3].[CH3:8][OH:9].[CH2:16]([O:15][C:13]([C:10]1[O:9][C:8]([CH2:7][N:6]2[C:5]3[CH:18]=[CH:19][CH:20]=[CH:21][C:4]=3[N:3]=[C:2]2[N:22]2[CH2:28][CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[CH:12][CH:11]=1)=[O:14])[CH3:17]

Participants

7

Reactant 4

HCID 1049PyridineHCID 68163Hexahydro-1,4-diazepineHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 184649721-(5-(ethoxycarbonyl)fur-2-ylmethyl)-2-chloro-1H-benzimidazole

Product 2

HCID 184646564-(1-(5-(ethoxycarbonyl)fur-2-ylmethyl)-1H-benzimidazol-2-yl)[1,4]diazepaneHCID 21705897Ammonia methanolYield 2%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Combine 2-chloro-1-(5-ethyoxycarbonylfur-2-ylmethyl)-1H-benzimidazole (9.50 g, 31.2 mmol) and [1,4]diazepane (6.24 g, 62.3 mmol), 1,8-diazabicyclo[5.4.0]undec-7-ene (5.6 mL, 37.4 mmol), and pyridine (90 mL). Heat to reflux. After 18 hours, cool to ambient temperature and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting sequentially with methanol and then 2% concentrated aqueous ammonia/methanol to give 4-(1-(5-ethyoxycarbonylfur-2-ylmethyl)-1H-benzimidazol-2-yl)[1,4]diazepane. Combine 4-(1-(5-ethyoxycarbonylfur-2-ylmethyl)-1H-benzimidazol-2-yl)[1,4]diazepane (1.0 g, 2.7 mmol) and tetrahydrofuran (10 mL). Add a solution of lithium aluminum hydride (2.7 mL, 1.0 M in tetrahydrofuran, 2.7 mmol). After 18 hours pour the reaction mixture into a beaker, dilute with dichloromethane, and cool to 0° C. With stirring add portionwise, Glauber's salt (Na2SO4.10H2O) until the evolution of gas ceases. Add dichloromethane to about double the volume, add celite, stir to form a thick slurry, and filter. Evaporate the filtrate in vacuo to give the title compound.

Workup

  1. temperatureHeat to reflux
  2. customevaporate in vacuo
  3. customto give a residue

Sources & evidence

ORD record
ord-8e89ea4cc3fb42138addb95323397149
Source dataset
uspto-grants-1999_08
Patent number
US05932571

Reaction notes

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