Dimethylformamide → Methyl 3-(3-(3-(6-(3-cyanopropyl)imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

HRID 570363Notes

Reaction equation

HRID 570363 reaction equation
[C:1]([CH2:3][CH2:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([C:12]([C:15]([OH:17])=O)=[CH:13][N:14]=2)[CH:11]=1)#[N:2].C(Cl)(=O)C(Cl)=O.CN(C=O)C.[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>[C:1]([CH2:3][CH2:4][CH2:5][C:6]1[CH:7]=[CH:8][C:9]2[N:10]([C:12]([C:15]([NH:29][C:30]3[CH:31]=[C:32]([C:37]4[N:41]=[C:40]([CH:42]5[CH2:45][N:44]([C:46]([O:48][CH3:49])=[O:47])[CH2:43]5)[O:39][N:38]=4)[CH:33]=[CH:34][C:35]=3[CH3:36])=[O:17])=[CH:13][N:14]=2)[CH:11]=1)#[N:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 712803346-(3-Cyanopropyl)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 71280972Methyl 3-(3-(3-(6-(3-cyanopropyl)imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-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-(3-cyanopropyl)imidazo[1,2-a]pyridine-3-carboxylic acid (25) (50 mg, 0.218 mmol) in anhydrous dichloromethane (2 mL) at 0° C. under Argon was added dropwise oxalyl chloride (20 μL, 0.240 mmol). Then, a drop of anhydrous DMF 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. To a mixture of the acid chloride and methyl 3-(3-(3-amino-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (31) (31 mg, 0.109 mmol) cooled to ° C. under Argon was added anhydrous pyridine (2 mL). The reaction was stirred to room temperature under Argon for 20 minutes. The solvent was concentrated. The crude product methyl 3-(3-(3-(6-(3-cyanopropyl)imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (F59) was purified by silica chromatography. 1H NMR (400 MHz, d6-DMSO) δ 10.13 (s, 1H), 9.38-9.36 (m, 1H), 8.66 (s, 1H), 8.11 (d, J=1.6 Hz, 1H), 7.86-7.82 (m, 2H), 7.63-7.60 (m, 1H), 7.51 (d, J=8.0 Hz, 1H), 4.39-4.34 (m, 2H), 4.31-4.24 (m, 1H), 4.21-4.18 (m, 2H), 3.59 (s, 3H), 2.81-2.77 (m, 2H), 2.60-2.52 (m, 2H), 2.38 (s, 3H), 1.97-1.90 (m 2H). MS m/z 500.52 (M+1)+.

Workup

  1. concentrationThe solvent was concentrated
  2. customthe crude solid was dried under vacuum
  3. temperaturecooled
  4. stirringThe reaction was stirred to room temperature under Argon for 20 minutes
  5. concentrationThe solvent was concentrated
  6. customThe crude product methyl 3-(3-(3-(6-(3-cyanopropyl)imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (F59) was purified by silica chromatography

Sources & evidence

ORD record
ord-c144812658624c13ac73b141750d62cf
Source dataset
uspto-grants-2015_05
Patent number
US09023839B2

Reaction notes

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