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

HRID 570366Notes

Reaction equation

HRID 570366 reaction equation
[C:1]([CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][C:8]2[N:9]([C:11]([C:14]([OH:16])=O)=[CH:12][N:13]=2)[CH:10]=1)#[N:2].C(Cl)(=O)C(Cl)=O.CN(C)C=O.[NH2:28][C:29]1[CH:30]=[C:31]([C:36]2[N:40]=[C:39]([CH:41]3[CH2:44][N:43]([C:45]([O:47][CH3:48])=[O:46])[CH2:42]3)[O:38][N:37]=2)[CH:32]=[CH:33][C:34]=1[CH3:35]>ClCCl.N1C=CC=CC=1>[C:1]([CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][C:8]2[N:9]([C:11]([C:14]([NH:28][C:29]3[CH:30]=[C:31]([C:36]4[N:40]=[C:39]([CH:41]5[CH2:44][N:43]([C:45]([O:47][CH3:48])=[O:46])[CH2:42]5)[O:38][N:37]=4)[CH:32]=[CH:33][C:34]=3[CH3:35])=[O:16])=[CH:12][N:13]=2)[CH:10]=1)#[N:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 712807766-(2-Cyanoethyl)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 71281430Methyl 3-(3-(3-(6-(2-cyanoethyl)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-(2-cyanoethyl)imidazo[1,2-a]pyridine-3-carboxylic acid (75) (50 mg, 0.232 mmol) in anhydrous dichloromethane (2 mL) at 0° C. under Argon was added dropwise oxalyl chloride (22 uL, 0.256 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 vacuo. Methyl 3-(3-(3-amino-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (31) (33 mg, 0.116 mmol) and anhydrous pyridine (2 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-(3-(6-(2-cyanoethyl)imidazo[1,2-a]pyridine-3-carboxamido)-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (F64). 1H NMR (400 MHz, d6-DMSO) δ 10.08 (s, 1H), 9.45 (s, 1H), 8.63 (s, 1H), 8.12 (d, J=1.6 Hz, 1H), 7.85 (dd, J=2.0, 5.6 Hz, 1H), 7.82 (d, J=6.8 Hz, 1H), 7.60 (dd, J=1.6, 9.2 Hz, 1H), 7.51 (d, J=8.0 Hz, 1H), 4.38-4.33 (m, 2H), 4.31-4.24 (m, 1H), 4.21-4.18 (m, 2H), 3.59 (s, 3H), 3.01 (t, J=7.6 Hz, 2H), 2.91 (t, J=6.4 Hz, 2H), 2.38 (s, 3H). MS m/z 486.18 (M+1)+.

Workup

  1. concentrationThe solvent was concentrated
  2. customthe crude solid was dried under vacuo
  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-676986d657f24d0bbfd775e863a28178
Source dataset
uspto-grants-2015_05
Patent number
US09023839B2

Reaction notes

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