1,1'-Carbonyldiimidazole → methyl 3-{(5S,7S)-7-[(6-cyano-1H-benzimidazol-1-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]dec-3-yl}-2,2-dimethylpropanoate

HRID 715498Notes

Reaction equation

HRID 715498 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[CH:9][N:8]([CH2:11][CH:12]3[CH2:17][CH2:16][CH2:15][C:14]([CH2:19][NH:20][CH2:21][C:22]([CH3:28])([CH3:27])[C:23]([O:25][CH3:26])=[O:24])([OH:18])[CH2:13]3)[C:7]=2[CH:29]=1)#[N:2].C1N=CN([C:35](N2C=NC=C2)=[O:36])C=1>O1CCOCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[CH:9][N:8]([CH2:11][C@H:12]3[CH2:17][CH2:16][CH2:15][C@:14]4([O:18][C:35](=[O:36])[N:20]([CH2:21][C:22]([CH3:27])([CH3:28])[C:23]([O:25][CH3:26])=[O:24])[CH2:19]4)[CH2:13]3)[C:7]=2[CH:29]=1)#[N:2]

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 71227554methyl 3-[({3-[(6-cyano-1H-benzimidazol-1-yl)methyl]-1-hydroxycyclohexaneyl}methyl)amino]-2,2-dimethylpropanoate

Product 1

HCID 71136167methyl 3-{(5S,7S)-7-[(6-cyano-1H-benzimidazol-1-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]dec-3-yl}-2,2-dimethylpropanoateYield 95%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of methyl 3-[({3-[(6-cyano-1H-benzimidazol-1-yl)methyl]-1-hydroxycyclohexaneyl}methyl)amino]-2,2-dimethylpropanoate (1.048 g, 2.63 mmol) and CDI (0.853 g, 5.26 mmol) in 1,4-dioxane (15 mL) was stirred at 100° C. for 1 day. The reaction was then concentrated and purified via silica gel chromatography (ISCO, 40 g silica gel column; solvent A=DCM; solvent B=MeOH (0.1M NH3); 0-5% B over 15 min; then 5% B over 5 min) to give methyl 3-{(5S,7S)-7-[(6-cyano-1H-benzimidazol-1-yl)methyl]-2-oxo-1-oxa-3-azaspiro[4.5]dec-3-yl}-2,2-dimethylpropanoate as a beige solid (1.06 g, 95% yield). MS (m/z) 425.2 (M+H+).

Workup

  1. concentrationThe reaction was then concentrated
  2. custompurified via silica gel chromatography (ISCO, 40 g silica gel column

Sources & evidence

ORD record
ord-303e7d2d43a34e7ca6abafa345c74d5a
Source dataset
uspto-grants-2015_11
Patent number
US09187464B2

Reaction notes

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