Dimethylformamide → N3-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3,6-dicarboxamide

HRID 1497927Notes

Reaction equation

HRID 1497927 reaction equation
[C:1]([C:4]1[CH:5]=[CH:6][C:7]2[N:8]([C:10]([C:13]([OH:15])=O)=[CH:11][N:12]=2)[CH:9]=1)(=[O:3])[NH2:2].C(Cl)(=O)C(Cl)=O.CN(C)C=O.C[NH:28][C:29]1[CH:34]=[C:33]([C:35]2[N:39]=[C:38]([CH:40]3[CH2:43][C:42]([F:45])([F:44])[CH2:41]3)[O:37][N:36]=2)[CH:32]=[CH:31][C:30]=1[CH3:46]>ClCCl.N1C=CC=CC=1>[F:45][C:42]1([F:44])[CH2:41][CH:40]([C:38]2[O:37][N:36]=[C:35]([C:33]3[CH:32]=[CH:31][C:30]([CH3:46])=[C:29]([NH:28][C:13]([C:10]4[N:8]5[CH:9]=[C:4]([C:1]([NH2:2])=[O:3])[CH:5]=[CH:6][C:7]5=[N:12][CH:11]=4)=[O:15])[CH:34]=3)[N:39]=2)[CH2:43]1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 679761586-Carbamoylimidazo[1,2-a]pyridine-3-carboxylic acidHCID 71280889Methyl 5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline

Product 1

HCID 71280471N3-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3,6-dicarboxamide

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirring suspension of 6-carbamoylimidazo[1,2-a]pyridine-3-carboxylic acid (110) (50 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. A stirring mixture of the acid chloride and methyl 5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylaniline (37) (23 mg, 0.0861 mmol) in anhydrous pyridine (2 mL) was stirred at room temperature for 20 minutes. The crude product was purified by reverse phase preparative HPLC to give N3-(5-(5-(3,3-difluorocyclobutyl)-1,2,4-oxadiazol-3-yl)-2-methylphenyl)imidazo[1,2-a]pyridine-3,6-dicarboxamide (F62). 1H NMR (400 MHz, d6-DMSO) δ 10.18 (s, 1H), 9.99-9.98 (m, 1H), 8.68 (s, 1H), 8.28 (s, 1H), 8.10 (d, J=1.6 Hz, 1H), 7.98 (dd, J=1.6, 9.2 Hz, 1H), 7.88-7.83 (m, 2H), 7.66 (s, 1H), 7.52 (d, J=8.0 Hz, 1H), 3.91-3.84 (m, 1H), 3.22-3.06 (m, 4H), 2.38 (s, 3H). MS m/z 452.14 (M+1)+.

Workup

  1. concentrationThe solvent was concentrated
  2. stirringwas stirred at room temperature for 20 minutes
  3. customThe crude product was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-e0d96b0a59604984a6a447fa1e3f73dc
Source dataset
uspto-grants-2015_12
Patent number
US09199981B2

Reaction notes

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