Oxalyl chloride → N-(5-cyano-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 570316Notes

Reaction equation

HRID 570316 reaction equation
[N:1]1[CH:2]=[C:3]([C:10]([OH:12])=O)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.C(Cl)(=O)C(Cl)=O.[NH2:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=1[F:28])[C:23]#[N:24]>ClCCl.CN(C=O)C.N1C=CC=CC=1>[C:23]([C:22]1[CH:25]=[CH:26][C:27]([F:28])=[C:20]([NH:19][C:10]([C:3]2[N:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]3=[N:1][CH:2]=2)=[O:12])[CH:21]=1)#[N:24]

Participants

7

Reactant 3

HCID 65578Oxalyl chlorideHCID 73142Imidazo(1,2-a)pyridine-3-carboxylic acidHCID 152516943-Amino-4-fluorobenzonitrile

Product 1

HCID 71280446N-(5-cyano-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirring suspension of imidazo[1,2-a]pyridine-3-carboxylic acid (1) (3.0 g, 18.5 mmol) in anhydrous dichloromethane (50 mL) at 0° C. was added dropwise oxalyl chloride (4.84 mL, 55.5 mmol). Then, three drops of anhydrous DMF was added and the reaction mixture was stirred at room temperature for 15 minutes. The solvent was concentrated and the crude solid was added to a stirring solution of 3-amino-4-fluorobenzonitrile (48) (2.5 g, 18.5 mmol) in anhydrous pyridine (50 mL) at room temperature. The reaction was stirred for 20 minutes and quenched with water (200 mL) with stirring for another 10 minutes. Then the precipitate was filtered and dried in air to yield N-(5-cyano-2-fluorophenyl)imidazo[1,2-a]pyridine-3-carboxamide (49). 1H NMR (400 MHz, d6-DMSO) δ 10.40 (s, 1H), 9.43 (td, J=1.2, 6.8 Hz, 1H), 8.63 (s, 1H), 8.21 (dd, J=2.0, 7.2 Hz, 1H), 7.78-7.84 (m, 2H), 7.54-7.63 (m, 2H), 7.22 (dt, J=1.2, 6.8, 1H). MS m/z 281.1 (M+1)+.

Workup

  1. concentrationThe solvent was concentrated
  2. stirringThe reaction was stirred for 20 minutes
  3. customquenched with water (200 mL)
  4. stirringwith stirring for another 10 minutes
  5. filtrationThen the precipitate was filtered
  6. customdried in air

Sources & evidence

ORD record
ord-5f8edd95c989405ebabe0a2ff3153a72
Source dataset
uspto-grants-2015_05
Patent number
US09023839B2

Reaction notes

Loading…