Dimethylformamide → HCID 71280951, compound

HRID 405853Notes

Reaction equation

HRID 405853 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][C:9]2[CH:10]=[CH:11][C:12]3[N:13]([C:15]([C:18]([OH:20])=O)=[CH:16][N:17]=3)[CH:14]=2)[CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[NH2:32][C:33]1[CH:34]=[C:35]([C:40]2[N:44]=[C:43]([CH:45]3[CH2:48][N:47]([C:49]([O:51][CH3:52])=[O:50])[CH2:46]3)[O:42][N:41]=2)[CH:36]=[CH:37][C:38]=1[CH3:39]>ClCCl.N1C=CC=CC=1>[CH3:39][C:38]1[CH:37]=[CH:36][C:35]([C:40]2[N:44]=[C:43]([CH:45]3[CH2:46][N:47]([C:49]([O:51][CH3:52])=[O:50])[CH2:48]3)[O:42][N:41]=2)=[CH:34][C:33]=1[NH:32][C:18]([C:15]1[N:13]2[CH:14]=[C:9]([CH2:8][CH2:7][N:4]3[CH2:3][CH2:2][O:1][CH2:6][CH2:5]3)[CH:10]=[CH:11][C:12]2=[N:17][CH:16]=1)=[O:20]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 71281298HCID 71281298, compoundHCID 86677444Methyl 3-(3-(3-amino-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

Product 1

HCID 71280951HCID 71280951, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirring suspension of 6-(2-morpholinoethyl)imidazo[1,2-a]pyridine-3-carboxylic acid (24l) (50 mg, 0.182 mmol) in anhydrous dichloromethane (2 mL) at 0° C. under Argon was added dropwise oxalyl chloride (17 uL, 0.200 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 3-(3-(3-amino-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (31) (26 mg, 0.0908 mmol) in anhydrous pyridine (1.5 mL) was stirred at room temperature for 2 hours. The crude product was purified by reverse phase preparative HPLC to give methyl 3-(3-(4-methyl-3-(6-(2-morpholinoethyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (F66). 1H NMR (400 MHz, d6-DMSO) δ 10.07 (s, 1H), 9.46 (s, 1H), 8.61 (s, 1H), 8.12 (d, J=1.6 Hz, 1H), 7.86-7.83 (m, 2H), 7.52-7.49 (m, 2H), 4.39-4.36 (m, 2H), 4.31-4.26 (m, 1H), 4.21-4.17 (m, 2H), 4.03-4.00 (m, 2H), 3.69-3.63 (m, 2H), 3.59 (s, 3H), 3.54-3.44 (m, 4H), 3.14-3.10 (m, 4H), 2.38 (s, 3H). MS m/z 546.24 (M+1)+.

Workup

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

Sources & evidence

ORD record
ord-1abe831bf1664cd6af6ef50374f00d32
Source dataset
uspto-grants-2014_06
Patent number
US08754071B2

Reaction notes

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