Methyl chloroformate → HCID 71281348, compound

HRID 1045482Notes

Reaction equation

HRID 1045482 reaction equation
[C:1]([N:8]1[CH2:11][CH:10]([C:12]([OH:14])=O)[CH2:9]1)([O:3][C:4](C)(C)C)=[O:2].C1N=CN(C(N2C=NC=C2)=O)C=1.O[N:28]=[C:29]([C:31]1[C:32]([CH3:50])=[CH:33][C:34]([CH3:49])=[C:35]([NH:37][C:38]([C:40]2[N:44]3[CH:45]=[CH:46][CH:47]=[CH:48][C:43]3=[N:42][CH:41]=2)=[O:39])[CH:36]=1)[NH2:30].ClC(OC)=O>CN1C(=O)CCC1.C(O)(C(F)(F)F)=O.O>[N:42]1[CH:41]=[C:40]([C:38]([NH:37][C:35]2[C:34]([CH3:49])=[CH:33][C:32]([CH3:50])=[C:31]([C:29]3[N:28]=[C:12]([CH:10]4[CH2:9][N:8]([C:1]([O:3][CH3:4])=[O:2])[CH2:11]4)[O:14][N:30]=3)[CH:36]=2)=[O:39])[N:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=12

Participants

8

Reactant 4

HCID 6586Methyl chloroformateHCID 682631,1'-CarbonyldiimidazoleHCID 27559811-Boc-Azetidine-3-carboxylic acidHCID 86677461HCID 86677461, compound

Product 1

HCID 71281348HCID 71281348, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6422Trifluoroacetic acidSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
125 °C

Procedure

To a stirring solution of Boc-azetidine-3-carboxylic acid (20 mg, 0.1 mmol) in anhydrous NMP (1 mL) was added CDI (16.3 mg, 0.1 mmol). The reaction was stirred for 10 minutes. Then, N-(5-(N′-hydroxycarbamimidoyl)-2,4-dimethylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (50c) (15 mg, 0.05 mmol) was added and the reaction was stirred for 15 minutes. The reaction was heated in the microwave at 125° C. for 15 minutes. The reaction mixture was added dropwise to water (20 mL) and extracted with EtOAc. The organic layers were combined, dried over Na2SO4, filtered and concentrated to afford a residue which was dissolved in 0.5 mL of TFA and stirred for 10 minutes. Then TFA was removed under vacuum and the residue was dissolved in DCM (1 mL) followed by addition of TEA (15 mg, 0.15 mmol) and methyl chloroformate (6 mg, 0.06 mmol). The solvent was removed and the residue was purified by HPLC to give methyl 3-(3-(5-(imidazo[1,2-a]pyridine-3-carboxamido)-2,4-dimethylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (F79). MS m/z 447.1 (M+1)+.

Workup

  1. stirringthe reaction was stirred for 15 minutes
  2. extractionextracted with EtOAc
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford a residue which
  7. stirringstirred for 10 minutes
  8. customThen TFA was removed under vacuum
  9. dissolutionthe residue was dissolved in DCM (1 mL)
  10. customThe solvent was removed
  11. customthe residue was purified by HPLC

Sources & evidence

ORD record
ord-2f5d2c1370ba4d1bae6e84c3ea8b075f
Source dataset
uspto-grants-2013_10
Patent number
US08569283B2

Reaction notes

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