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 1045474Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1045474
[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]

Komponenten

7

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1049PyridineLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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)+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-8512e9f77a6b4741b97509d250187c00
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08569283B2

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