Dimethylformamide → Methyl 3-(3-(4-methyl-3-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

HRID 1045473Notes

Reaction equation

HRID 1045473 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:11]([OH:13])=O)=[CH:9][N:10]=2)[CH:7]=1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[NH2:25][C:26]1[CH:27]=[C:28]([C:33]2[N:37]=[C:36]([CH:38]3[CH2:41][N:40]([C:42]([O:44][CH3:45])=[O:43])[CH2:39]3)[O:35][N:34]=2)[CH:29]=[CH:30][C:31]=1[CH3:32]>ClCCl.N1C=CC=CC=1>[CH3:32][C:31]1[CH:30]=[CH:29][C:28]([C:33]2[N:37]=[C:36]([CH:38]3[CH2:39][N:40]([C:42]([O:44][CH3:45])=[O:43])[CH2:41]3)[O:35][N:34]=2)=[CH:27][C:26]=1[NH:25][C:11]([C:8]1[N:6]2[CH:7]=[C:2]([CH3:1])[CH:3]=[CH:4][C:5]2=[N:10][CH:9]=1)=[O:13]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 552681936-Methylimidazo[1,2-a]pyridine-3-carboxylic acidHCID 86677444Methyl 3-(3-(3-amino-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

Product 1

HCID 71280978Methyl 3-(3-(4-methyl-3-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirring suspension of 6-methylimidazo[1,2-a]pyridine-3-carboxylic acid (24j) (35 mg, 0.196 mmol) in anhydrous dichloromethane (2 mL) at 0° C. under Argon was added dropwise oxalyl chloride (17 uL, 0.206 mmol). Then, a drop of anhydrous N,N-dimethylformamide was added and the reaction mixture was stirred at 0° C. for 1 hour. The solvent was concentrated. A stirring mixture of the acid chloride and methyl 3-(3-(3-amino-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (31) (28 mg, 0.098 mmol) in anhydrous pyridine (1.5 mL) was stirred at room temperature for 2 hours. The solvent was concentrated and the crude product was purified by silica chromatography to give methyl 3-(3-(4-methyl-3-(6-methylimidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (F62). 1H NMR (400 MHz, d6-DMSO) δ 10.15 (s, 1H), 9.36 (s, 1H), 8.67 (s, 1H), 8.11 (d, J=2.0 Hz, 1H), 7.85 (dd, J=2.0, 8.0 Hz, 1H), 7.81 (d, J=9.2 Hz, 1H), 7.57 (dd, J=1.2, 9.2 Hz, 1H), 7.51 (d, J=8.0 Hz, 1H), 4.39-4.34 (m, 2H), 4.31-4.24 (m, 1H), 4.22-4.17 (m, 2H), 3.59 (s, 3H), 2.41 (s, 3H), 2.37 (s, 3H). MS m/z 447.17 (M+1)+.

Workup

  1. concentrationThe solvent was concentrated
  2. stirringwas stirred at room temperature for 2 hours
  3. concentrationThe solvent was concentrated
  4. customthe crude product was purified by silica chromatography

Sources & evidence

ORD record
ord-d8e1469829344cf5a83ea53547b8655c
Source dataset
uspto-grants-2013_10
Patent number
US08569283B2

Reaction notes

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