Isopropylamine → 1-(diphenylmethyl)-N-(1-methylethyl)-3-[(phenylmethyl)amino]azetidine-3-carboxamide

HRID 1808978Notes

Reaction equation

HRID 1808978 reaction equation
[C:1]1([CH:7]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:8]2[CH2:11]C(NCC3C=CC=CC=3)(C(O)=O)[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([N:32](CC)[CH:33]([CH3:35])[CH3:34])(C)C.C[CH:39]([NH2:41])[CH3:40].C([O:45][CH2:46][CH3:47])(=O)C>CN(C=O)C>[C:23]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]2[CH2:9][C:47]([NH:41][CH2:39][C:40]3[CH:5]=[CH:6][CH:1]=[CH:2][CH:3]=3)([C:46]([NH:32][CH:33]([CH3:34])[CH3:35])=[O:45])[CH2:11]2)[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

6

Reactant 4

HCID 6363IsopropylamineHCID 8857Ethyl AcetateHCID 81531DiisopropylethylamineHCID 219058151-(Diphenylmethyl)-3-[(phenylmethyl)amino]azetidine-3-carboxylic acid

Product 1

HCID 670518131-(diphenylmethyl)-N-(1-methylethyl)-3-[(phenylmethyl)amino]azetidine-3-carboxamideYield 92%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-(diphenylmethyl)-3-[(phenylmethyl)amino]azetidine-3-carboxylic acid (0.50 g, 1.34 mmol), N,N-diisopropylethylamine (0.47 mL, 2.68 mmol) in DMF (3 mL) was added 1-benzotriazolyloxytripyrrolidinylphosphonium hexafluorophosphate (1.34 g, 2.68 mol) and the resulting mixture was stirred at room temperature for 10 minutes. To this mixture was added 2-propylamine (0.22 mL, 2.68 mmol) and stirring was continued for 18 h. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with 2% aqueous citric acid, 5% lithium chloride, and brine solutions (50 mL each), dried over sodium sulfate, filtered and concentrated to give an oily residue which was purified by flash chromatography (silica gel, eluting with 15-25% ethyl acetate-hexane) to give 1-(diphenylmethyl)-N-(1-methylethyl)-3-[(phenylmethyl)amino]azetidine-3-carboxamide (0.51 g, 92% yield), MS (EI) for C27H31N3O: 414 (MH+).

Workup

  1. stirringstirring
  2. waitwas continued for 18 h
  3. washwashed with 2% aqueous citric acid, 5% lithium chloride, and brine solutions (50 mL each)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give an oily residue which
  8. customwas purified by flash chromatography (silica gel, eluting with 15-25% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-99cc8d7e570b41c6877f0ad552d5e601
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

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