Dimethylformamide → Methyl 3-(3-(4-methyl-3-(7-(3-oxobutyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

HRID 1045479ノート

反応式

HRID 1045479 の反応式
[O:1]=[C:2]([CH3:17])[CH2:3][CH2:4][C:5]1[CH:10]=[CH:9][N:8]2[C:11]([C:14]([OH:16])=O)=[CH:12][N:13]=[C:7]2[CH:6]=1.C(Cl)(=O)C(Cl)=O.CN(C)C=O.[NH2:29][C:30]1[CH:31]=[C:32]([C:37]2[N:41]=[C:40]([CH:42]3[CH2:45][N:44]([C:46]([O:48][CH3:49])=[O:47])[CH2:43]3)[O:39][N:38]=2)[CH:33]=[CH:34][C:35]=1[CH3:36]>ClCCl.N1C=CC=CC=1>[CH3:36][C:35]1[CH:34]=[CH:33][C:32]([C:37]2[N:41]=[C:40]([CH:42]3[CH2:43][N:44]([C:46]([O:48][CH3:49])=[O:47])[CH2:45]3)[O:39][N:38]=2)=[CH:31][C:30]=1[NH:29][C:14]([C:11]1[N:8]2[CH:9]=[CH:10][C:5]([CH2:4][CH2:3][C:2](=[O:1])[CH3:17])=[CH:6][C:7]2=[N:13][CH:12]=1)=[O:16]

参加物

7

反応物 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 712808037-(3-Oxobutyl)imidazo[1,2-a]pyridine-3-carboxylic acidHCID 86677444Methyl 3-(3-(3-amino-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

生成物 1

HCID 71280991Methyl 3-(3-(4-methyl-3-(7-(3-oxobutyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a stirring suspension of 7-(3-oxobutyl)imidazo[1,2-a]pyridine-3-carboxylic acid (86) (40 mg, 0.172 mmol) in anhydrous dichloromethane (2 mL) at 0° C. under Argon was added dropwise oxalyl chloride (16 uL, 0.189 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 vacuum. Methyl 3-(3-(3-amino-4-methylphenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (31) (25 mg, 0.086 mmol) and anhydrous pyridine (1 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-(4-methyl-3-(7-(3-oxobutyl)imidazo[1,2-a]pyridine-3-carboxamido)phenyl)-1,2,4-oxadiazol-5-yl)azetidine-1-carboxylate (F73). 1H NMR (400 MHz, d6-DMSO) δ 10.24 (s, 1H), 9.44-9.41 (m, 1H), 8.73 (s, 1H), 8.09 (d, J=1.6 Hz, 1H), 7.85 (dd, J=1.6, 8.0 Hz, 1H), 7.73 (s, 1H), 7.51 (d, J=8.4 Hz, 1H), 7.32-7.29 (m, 1H), 4.39-4.35 (m, 2H), 4.31-4.24 (m, 1H), 4.21-4.17 (m, 2H), 3.59 (s, 3H), 2.98-2.91 (m, 4H), 2.37 (s, 3H), 2.13 (s, 3H). MS m/z 503.2 (M+1)+.

後処理

  1. concentrationThe solvent was concentrated
  2. customthe crude solid was dried under vacuum
  3. stirringThe reaction was stirred to room temperature under Argon for 20 minutes
  4. customThe crude product was purified by reverse phase preparative HPLC

出典と根拠

ORDレコード
ord-ad0e5afb16b04c879c6b793761639026
出典データセット
uspto-grants-2013_10
特許番号
US08569283B2

反応ノート

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