Azetidine → HCID 71288703, compound

HRID 1621114Notes

Reaction equation

HRID 1621114 reaction equation
[CH3:1][N:2]1[C:6]([C:7](=[O:23])[NH:8][CH2:9][CH2:10][C:11]2[N:12]([CH3:22])[CH:13]=[C:14]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:15]=2)=[C:5]([C:24]([OH:26])=O)[N:4]=[C:3]1[CH3:27].F[P-](F)(F)(F)(F)F.C(C(=NO[C+](N(C)C)[N:46]1[CH2:51][CH2:50]OC[CH2:47]1)C(OCC)=O)#N.C(N(CC)C(C)C)(C)C.N1CCC1>CN(C=O)C>[CH3:22][N:12]1[CH:13]=[C:14]([C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:15]=[C:11]1[CH2:10][CH2:9][NH:8][C:7]([C:6]1[N:2]([CH3:1])[C:3]([CH3:27])=[N:4][C:5]=1[C:24]([N:46]1[CH2:47][CH2:50][CH2:51]1)=[O:26])=[O:23]

Participants

6

Reactant 4

HCID 10422AzetidineHCID 81531Diisopropylethylamine2×HCID 71279194HCID 71279194, compoundHCID 178472143HCID 178472143, compound

Product 1

HCID 71288703HCID 71288703, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1,2-dimethyl-5-(2-(1-methyl-4-phenyl-1H-imidazol-2-yl)ethylcarbamoyl)-1H-imidazole-4-carboxylic acid (30 mg, 81.7 μmol) in DMF (1 mL) were added under nitrogen atmosphere at 0-5° C. (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate (COMU; 38.5 mg, 89.8 μmol) and N,N-diisopropylethylamine (14.3 μL, 81.7 μmol). After stirring for 5 min, azetidine (6.18 μL, 89.8 μmol) and N,N-diisopropylethylamine (14.3 μL, 81.7 μmol) were added, the ice bath was removed after additional 10 min and the reaction mixture was stirred at RT for 2 h. The product was obtained after purification by preparative HPLC using an acetonitrile/water (containing 0.1% formic acid) gradient as colorless waxy solid (1.9 mg, 4.67 μmol, 5.72%). MS: M=407.4 (M+H)+

Workup

  1. customthe ice bath was removed after additional 10 min
  2. stirringthe reaction mixture was stirred at RT for 2 h
  3. customThe product was obtained
  4. customafter purification by preparative HPLC

Sources & evidence

ORD record
ord-16b040345b074edcb9c5d9c3358d36b6
Source dataset
uspto-grants-2014_07
Patent number
US08772510B2

Reaction notes

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