Diisopropylethylamine → 2-(dimethylamino)-2-oxoethyl (3S)-2-(4-{[bis(1H-imidazol-2-ylmethyl)amino]methyl}benzyl)-8-(2,2-dimethylpropyl)-2,8-diazaspiro[4.5]decane-3-carboxylate

HRID 445238Notes

Reaction equation

HRID 445238 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][N:7]([CH2:14][C:15]1[CH:39]=[CH:38][C:18]([CH2:19][N:20]2[C@H:24]([C:25]([OH:27])=[O:26])[CH2:23][C:22]3([CH2:32][CH2:31][N:30]([CH2:33][C:34]([CH3:37])([CH3:36])[CH3:35])[CH2:29][CH2:28]3)[CH2:21]2)=[CH:17][CH:16]=1)[CH2:8][C:9]1[NH:10][CH:11]=[CH:12][N:13]=1.O[CH2:41][C:42]([N:44]([CH3:46])[CH3:45])=[O:43].C(N(C(C)C)CC)(C)C.C(=O)([O-])O.[Na+]>CN(C)C=O>[NH:1]1[CH:5]=[CH:4][N:3]=[C:2]1[CH2:6][N:7]([CH2:14][C:15]1[CH:16]=[CH:17][C:18]([CH2:19][N:20]2[C@H:24]([C:25]([O:27][CH2:41][C:42]([N:44]([CH3:46])[CH3:45])=[O:43])=[O:26])[CH2:23][C:22]3([CH2:32][CH2:31][N:30]([CH2:33][C:34]([CH3:35])([CH3:36])[CH3:37])[CH2:29][CH2:28]3)[CH2:21]2)=[CH:38][CH:39]=1)[CH2:8][C:9]1[NH:13][CH:12]=[CH:11][N:10]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 128746822-Hydroxy-N,N-dimethylacetamideHCID 67285755(3S)-2-(4-{[bis(1H-imidazol-2-ylmethyl)amino]methyl}benzyl)-8-(2,2-dimethylpropyl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid

Product 1

HCID 866644662-(dimethylamino)-2-oxoethyl (3S)-2-(4-{[bis(1H-imidazol-2-ylmethyl)amino]methyl}benzyl)-8-(2,2-dimethylpropyl)-2,8-diazaspiro[4.5]decane-3-carboxylateYield 73.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an N,N-dimethylformamide (1 mL) solution of the compound (80 mg) obtained in Example 32(5), 2-hydroxy-N,N-dimethylacetoamide (CAS Registry Number: 14658-93-6; 77 mg), diisopropylethylamine (39 μL) and N,N,N′,N′-tetramethyl-O-(7-azobenzotriazol-1-yl)uronium hexafluorophosphate (86 mg) were added. The reaction solution was stirred at room temperature for 16 hours. To this solution, an aqueous saturated sodium hydrogen carbonate solution was added, and the solution was extracted with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (CHROMATOREX NH (trade name), manufactured by Fuji Silysia Chemical Ltd.) (ethyl acetate:methanol=1:0→30:1→15:1) to obtain the title compound (68 mg) having the following physical properties.

Workup

  1. extractionthe solution was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography (CHROMATOREX NH (trade name), manufactured by Fuji Silysia Chemical Ltd.) (ethyl acetate:methanol=1:0→30:1→15:1)

Sources & evidence

ORD record
ord-f426e78d9fcd4042b1142f6aacec342f
Source dataset
uspto-grants-2013_07
Patent number
US08476290B2

Reaction notes

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