Methyl 3-amino-2,2-dimethylpropanoate → methyl 3-[({3-[(6-cyano-1H-benzimidazol-1-yl)methyl]-1-hydroxycyclohexaneyl}methyl)amino]-2,2-dimethylpropanoate

HRID 715497Notes

Reaction equation

HRID 715497 reaction equation
[O:1]1[C:3]2([CH2:8][CH2:7][CH2:6][C@H:5]([CH2:9][N:10]3[C:14]4[CH:15]=[C:16]([C:19]#[N:20])[CH:17]=[CH:18][C:13]=4[N:12]=[CH:11]3)[CH2:4]2)[CH2:2]1.[NH2:21][CH2:22][C:23]([CH3:29])([CH3:28])[C:24]([O:26][CH3:27])=[O:25]>C(O)(C)C>[C:19]([C:16]1[CH:17]=[CH:18][C:13]2[N:12]=[CH:11][N:10]([CH2:9][CH:5]3[CH2:6][CH2:7][CH2:8][C:3]([CH2:2][NH:21][CH2:22][C:23]([CH3:29])([CH3:28])[C:24]([O:26][CH3:27])=[O:25])([OH:1])[CH2:4]3)[C:14]=2[CH:15]=1)#[N:20]

Participants

4

Reactant 2

HCID 13285789Methyl 3-amino-2,2-dimethylpropanoateHCID 893898341-[(55)-1-oxaspiro[2.5]oct-5-ylmethyl]-1H-benzimidazole-6-carbonitrile

Product 1

HCID 71227554methyl 3-[({3-[(6-cyano-1H-benzimidazol-1-yl)methyl]-1-hydroxycyclohexaneyl}methyl)amino]-2,2-dimethylpropanoateYield 66.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 1-[(55)-1-oxaspiro[2.5]oct-5-ylmethyl]-1H-benzimidazole-6-carbonitrile (1.064 g, 3.98 mmol) and methyl 3-amino-2,2-dimethylpropanoate (0.679 g, 5.17 mmol) in isopropanol (13.27 mL) was stirred at 100° C. for 1 day. Reaction was concentrated and purified via silica gel chromatography (ISCO, 120 g silica gel column. Solvent A was DCM and solvent B was 0.1M NH3 in MeOH; 0-10% B over 15 min; 10% B over 6 min) to give methyl 3-[({3-[(6-cyano-1H-benzimidazol-1-yl)methyl]-1-hydroxycyclohexaneyl}methyl)amino]-2,2-dimethylpropanoate as a sticky solid (1.05 g, 66.1% yield). MS (m/z) 399.2 (M+H+).

Workup

  1. customReaction
  2. concentrationwas concentrated
  3. custompurified via silica gel chromatography (ISCO, 120 g silica gel column. Solvent A was DCM and solvent B was 0.1M NH3 in MeOH; 0-10% B over 15 min; 10% B over 6 min)

Sources & evidence

ORD record
ord-c767df2b8dd44205b1059d2fd7559944
Source dataset
uspto-grants-2015_11
Patent number
US09187464B2

Reaction notes

Loading…