1-Hydroxybenzotriazole → 4-[2-fluoro-4-(7-quinolinyl)phenyl]-5-({1-[(1-methylcyclopropyl)carbonyl]-3-azetidinyl}methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 525226ノート

反応式

HRID 525226 の反応式
[NH:1]1[CH2:4][CH:3]([CH2:5][C:6]2[N:7]([C:12]3[CH:17]=[CH:16][C:15]([C:18]4[CH:27]=[C:26]5[C:21]([CH:22]=[CH:23][CH:24]=[N:25]5)=[CH:20][CH:19]=4)=[CH:14][C:13]=3[F:28])[C:8](=[O:11])[NH:9][N:10]=2)[CH2:2]1.[CH3:29][C:30]1([C:33](O)=[O:34])[CH2:32][CH2:31]1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.N1(O)C2C=CC=CC=2N=N1>CN(C)C=O>[F:28][C:13]1[CH:14]=[C:15]([C:18]2[CH:27]=[C:26]3[C:21]([CH:22]=[CH:23][CH:24]=[N:25]3)=[CH:20][CH:19]=2)[CH:16]=[CH:17][C:12]=1[N:7]1[C:6]([CH2:5][CH:3]2[CH2:4][N:1]([C:33]([C:30]3([CH3:29])[CH2:32][CH2:31]3)=[O:34])[CH2:2]2)=[N:10][NH:9][C:8]1=[O:11]

参加物

7

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 813261-Methylcyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 673759915-(3-azetidinylmethyl)-4-[2-fluoro-4-(7-quinolinyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

生成物 1

HCID 673558204-[2-fluoro-4-(7-quinolinyl)phenyl]-5-({1-[(1-methylcyclopropyl)carbonyl]-3-azetidinyl}methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one収率 9.2%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

In a round bottom flask under nitrogen, a solution of 5-(3-azetidinylmethyl)-4-[2-fluoro-4-(7-quinolinyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (1.07 mmol) in N,N-dimethylformamide (5 mL) was treated with 1-methylcyclopropanecarboxylic acid (1.285 mmol), N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (2.14 mmol), N,N-diisopropylethylamine (3.21 mmol) and then 1H-1,2,3-benzotriazol-1-ol (2.14 mmol). The reaction mixture was stirred at room temperature for 1.5 h and then concentrated in vacuo. Purification of the residue by reverse phase HPLC (10-70% acetonitrile/water with 0.1% NH4OH) and subsequent silica gel chromatography (0-3% methanol/ethyl acetate) followed by trituration in ethanol provided the title compound as a white solid (45 mg, 9.2%). MS(ES)+ m/e 458.2 [M+H]+.

後処理

  1. concentrationconcentrated in vacuo
  2. customPurification of the residue by reverse phase HPLC (10-70% acetonitrile/water with 0.1% NH4OH) and subsequent silica gel chromatography (0-3% methanol/ethyl acetate)

出典と根拠

ORDレコード
ord-5631904e7ea242779850c8303f4f5ec8
出典データセット
uspto-grants-2016_05
特許番号
US09340529B2

反応ノート

読み込み中…