Dimethylformamide → Methyl 3-(3-(4-methyl-3-(7-(3-oxobutyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

HRID 1045479Notes

Reaction equation

HRID 1045479 reaction equation
[O:1]=[C:2]([CH3:17])[CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][N:8]2[C:11]([C:14]([OH:16])=O)=[CH:12][N:13]=[C:7]2[CH:6]=1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[NH2:29][C:30]1[CH:31]=[C:32]([C:37]2[N:41]=[C:40]([CH:42]3[CH2:45][N:44]([C:46]([O:48][CH3:49])=[O:47])[CH2:43]3)[O:39][N:38]=2)[CH:33]=[CH:34][C:35]=1[CH3:36]>ClCCl.N1C=CC=CC=1>[CH3:36][C:35]1[CH:34]=[CH:33][C:32]([C:37]2[N:41]=[C:40]([CH:42]3[CH2:43][N:44]([C:46]([O:48][CH3:49])=[O:47])[CH2:45]3)[O:39][N:38]=2)=[CH:31][C:30]=1[NH:29][C:14]([C:11]1[N:8]2[CH:9]=[CH:10][C:5]([CH2:4][CH2:3][C:2](=[O:1])[CH3:17])=[CH:6][C:7]2=[N:13][CH:12]=1)=[O:16]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 712808037-(3-Oxobutyl)imidazo[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 71280991Methyl 3-(3-(4-methyl-3-(7-(3-oxobutyl)imidazo[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 7-(3-oxobutyl)imidazo[1,2-a]pyridine-3-carboxylic acid (86) (40 mg, 0.172 mmol) in anhydrous dichloromethane (2 mL) at 0° C. under Argon was added dropwise oxalyl chloride (16 uL, 0.189 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 and the crude solid was dried under vacuum. Methyl 3-(3-(3-amino-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (31) (25 mg, 0.086 mmol) and anhydrous pyridine (1 mL) were added to the acid chloride. The reaction was stirred to room temperature under Argon for 20 minutes. The crude product was purified by reverse phase preparative HPLC to give methyl 3-(3-(4-methyl-3-(7-(3-oxobutyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (F73). 1H NMR (400 MHz, d6-DMSO) δ 10.24 (s, 1H), 9.44-9.41 (m, 1H), 8.73 (s, 1H), 8.09 (d, J=1.6 Hz, 1H), 7.85 (dd, J=1.6, 8.0 Hz, 1H), 7.73 (s, 1H), 7.51 (d, J=8.4 Hz, 1H), 7.32-7.29 (m, 1H), 4.39-4.35 (m, 2H), 4.31-4.24 (m, 1H), 4.21-4.17 (m, 2H), 3.59 (s, 3H), 2.98-2.91 (m, 4H), 2.37 (s, 3H), 2.13 (s, 3H). MS m/z 503.2 (M+1)+.

Workup

  1. concentrationThe solvent was concentrated
  2. customthe crude solid was dried under vacuum
  3. stirringThe reaction was stirred to room temperature under Argon for 20 minutes
  4. customThe crude product was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-ad0e5afb16b04c879c6b793761639026
Source dataset
uspto-grants-2013_10
Patent number
US08569283B2

Reaction notes

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