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

HRID 570360Notes

Reaction equation

HRID 570360 reaction equation
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:4]=[CH:5][C:6]2[N:7]([C:9]([C:12]([OH:14])=O)=[CH:10][N:11]=2)[CH:8]=1.C(Cl)(=O)C(Cl)=O.CN(C=O)C.[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>[CH3:35][C:34]1[CH:33]=[CH:32][C:31]([C:36]2[N:40]=[C:39]([CH:41]3[CH2:42][N:43]([C:45]([O:47][CH3:48])=[O:46])[CH2:44]3)[O:38][N:37]=2)=[CH:30][C:29]=1[NH:28][C:12]([C:9]1[N:7]2[CH:8]=[C:3]([C:2]([F:1])([F:16])[F:15])[CH:4]=[CH:5][C:6]2=[N:11][CH:10]=1)=[O:14]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 510720316-(Trifluoromethyl)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 71281213Methyl 3-(3-(4-methyl-3-(6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirring suspension of 6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxylic acid (24a) (50 mg, 0.217 mmol) in anhydrous dichloromethane (2 mL) at 0° C. under Argon was added dropwise oxalyl chloride (19 μL, 0.228 mmol). Then, a drop of anhydrous DMF was added and the reaction mixture was stirred at room temperature for 1.5 hours. The solvent was concentrated and the crude solid was added portion-wise to a stirring solution of methyl 3-(3-(3-amino-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (31) (47 mg, 0.163 mmol) in anhydrous pyridine (1 mL) at 0° C. The reaction was stirred at room temperature under Argon for 10 minutes and quenched with water. The crude product was purified by preparative HPLC to yield methyl 3-(3-(4-methyl-3-(6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (F52). 1H NMR (400 MHz, d6-DMSO) δ 10.27 (s, 1H), 9.90-9.85 (m, 1H), 8.72 (s, 1H), 8.08 (d, J=1.6 Hz, 1H), 8.02-7.99 (m, 1H), 7.86 (dd, J=2.0, 8.0 Hz, 1H), 7.79 (dd, J=2.0, 9.2 Hz, 1H), 7.52 (d, J=8.0 Hz, 1H), 4.37-4.19 (m, 5H), 3.59 (s, 3H), 2.37 (s, 3H). MS m/z 501.43 (M+1)+.

Workup

  1. concentrationThe solvent was concentrated
  2. stirringThe reaction was stirred at room temperature under Argon for 10 minutes
  3. customquenched with water
  4. customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-ebff8cb09f4144ec829ecf5f898c36e4
Source dataset
uspto-grants-2015_05
Patent number
US09023839B2

Reaction notes

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