Diisopropylethylamine → N-[{(2S)-4-(3,4-Dichlorobenzyl)morpholin-2-yl]methyl}-2-(5-phenyl-2H-tetraazol-2-yl)acetamide

HRID 2212013Notes

Reaction equation

HRID 2212013 reaction equation
[C:1]1([C:7]2[N:8]=[N:9][N:10]([CH2:12][C:13]([OH:15])=O)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)C(C)C)(C)C.[Cl:25][C:26]1[CH:27]=[C:28]([CH:38]=[CH:39][C:40]=1[Cl:41])[CH2:29][N:30]1[CH2:35][CH2:34][O:33][C@@H:32]([CH2:36][NH2:37])[CH2:31]1>CN(C)C=O>[Cl:25][C:26]1[CH:27]=[C:28]([CH:38]=[CH:39][C:40]=1[Cl:41])[CH2:29][N:30]1[CH2:35][CH2:34][O:33][C@@H:32]([CH2:36][NH:37][C:13](=[O:15])[CH2:12][N:10]2[N:9]=[N:8][C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[N:11]2)[CH2:31]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 10865632-(5-phenyl-2H-1,2,3,4-tetrazol-2-yl)acetic acidHCID 10171585(S)-(4-(3,4-Dichlorobenzyl)morpholin-2-YL)methanamine

Product 1

HCID 68883559N-[{(2S)-4-(3,4-Dichlorobenzyl)morpholin-2-yl]methyl}-2-(5-phenyl-2H-tetraazol-2-yl)acetamideYield 99.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
22 °C

Procedure

A solution of (5-phenyl-2H-tetraazol-2-yl)acetic acid (0.082 g) in N,N-dimethylformamide (2 ml) under nitrogen was treated with O-(7-azabenzotriazol-1-yl)-N,N,N′N′-tetramethylammonium hexafluorophosphate (0.152 g) and N,N-diisopropylethylamine (0.139 ml) followed by a solution of Intermediate 9 (0.110 g) in N,N-dimethylformamide (3 ml), and the mixture was stirred at 22° C. for 4 h. The solvent was removed in vacuo and the residue dissolved in ethyl acetate (20 ml). The solution was washed with 10% aqueous citric acid (20 ml), brine (20 ml), saturated aqueous sodium hydrogen carbonate (20 ml) and brine (20 ml), dried (MgSO4) and evaporated in vacuo. Purification by flash chromatography on silica gel (Merck 9385), eluting with ethyl acetate, followed by trituration of the resultant product with diethyl ether, gave the title compound as a white solid (0.184 g).

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue dissolved in ethyl acetate (20 ml)
  3. washThe solution was washed with 10% aqueous citric acid (20 ml), brine (20 ml), saturated aqueous sodium hydrogen carbonate (20 ml) and brine (20 ml)
  4. dry with materialdried (MgSO4)
  5. customevaporated in vacuo
  6. customPurification by flash chromatography on silica gel (Merck 9385)
  7. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-d4ce371150474eae973372f60c85500e
Source dataset
uspto-grants-2006_09
Patent number
US07101882B2

Reaction notes

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