1-Hydroxybenzotriazole → 1-[2-(3,5-Dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid methyl-(4-methyl-benzyl)-amide

HRID 408597

Reaction equation

HRID 408597 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([N:12]2[CH2:15][CH2:14][C:13]2([CH3:19])[C:16]([OH:18])=O)=[O:11])[CH:5]=[C:6]([CH3:8])[CH:7]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[CH3:42][NH:43][CH2:44][C:45]1[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=1>CN(C=O)C.C1COCC1.C(Cl)Cl>[CH3:42][N:43]([CH2:44][C:45]1[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=1)[C:16]([C:13]1([CH3:19])[CH2:14][CH2:15][N:12]1[C:10](=[O:11])[CH2:9][C:4]1[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([CH3:1])[CH:3]=1)=[O:18]

Participants

8

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2794640N-Methyl-4-methylbenzylamineHCID 705580721-[2-(3,5-Dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid

Product 1

HCID 705573251-[2-(3,5-Dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid methyl-(4-methyl-benzyl)-amide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of Intermediate 119 1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid (1 eq.) in either DCM, THF or DMF was added HOBt (1.1 eq.), EDC.HCl (1.5 eq.), TEA (3 eq.) and methyl-(4-methyl benzyl)-amine (1.5 eq.). The reaction was stirred at 20° C. for 15 h, then the crude was concentrated under reduced pressure and partitioned between a saturated aqueous solution of NaHCO3 and EtOAc. The aqueous layer was extracted three times with EtOAc. The organic layers were combined, washed with water then with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with DCM/MeOH: 100/0 to 99/1) to afford 1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid methyl-(4-methyl-benzyl)-amide.

Workup

  1. concentrationthe crude was concentrated under reduced pressure
  2. custompartitioned between a saturated aqueous solution of NaHCO3 and EtOAc
  3. extractionThe aqueous layer was extracted three times with EtOAc
  4. washwashed with water
  5. dry with materialwith brine, dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude was purified by chromatography on silica gel (elution with DCM/MeOH: 100/0 to 99/1)

Sources & evidence

ORD record
ord-269bd3c177f04cafbeeca40885a0f210
Source dataset
uspto-grants-2014_06
Patent number
US08759334B2

Linked notes

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