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

HRID 525254ノート

反応式

HRID 525254 の反応式
[F:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[CH:13][CH:14]=[N:15]3)=[CH:10][CH:9]=2)[CH:5]=[CH:4][C:3]=1[N:18]1[C:22](=[O:23])[NH:21][N:20]=[C:19]1[CH2:24][C@@H:25]1[CH2:29][CH2:28][N:27]([C:30](OC(C)(C)C)=[O:31])[CH2:26]1.[CH3:37][C:38]1(C(O)=O)[CH2:40][CH2:39]1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C>O1CCOCC1>[F:1][C:2]1[CH:7]=[C:6]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[CH:13][CH:14]=[N:15]3)=[CH:10][CH:9]=2)[CH:5]=[CH:4][C:3]=1[N:18]1[C:19]([CH2:24][C@@H:25]2[CH2:29][CH2:28][N:27]([C:30]([C:38]3([CH3:37])[CH2:40][CH2:39]3)=[O:31])[CH2:26]2)=[N:20][NH:21][C:22]1=[O:23]

参加物

7

反応物 5

HCID 757711-HydroxybenzotriazoleHCID 813261-Methylcyclopropanecarboxylic acidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 673549061,1-dimethylethyl (3S)-3-({4-[2-fluoro-4-(7-quinolinyl)phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl)-1-pyrrolidinecarboxylate

生成物 1

HCID 673536464-[2-fluoro-4-(7-quinolinyl)phenyl]-5-({(3S)-1-[(1-methylcyclopropyl)carbonyl]-3-pyrrolidinyl}methyl)-2,4-dihydro-3H-1,2,4-triazol-3-one収率 59.5%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

実験手順

Into a 50 mL round bottom flask was placed 1,1-dimethylethyl (3S)-3-({4-[2-fluoro-4-(7-quinolinyl)phenyl]-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl}methyl)-1-pyrrolidinecarboxylate (0.082 mmol). Added was 4N HCL in dioxane (1.0 mL). The solution was stirred at room temperature for 1 h and then was concentrated in vacuo. The solid was taken up in N,N-dimethylformamide (1 mL). Added to flask was 1-methylcyclopropanecarboxylic acid (0.100 mmol), 1-hydroxybenzotriazole (0.196 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.183 mmol), and N,N-diisopropylethylamine (0.286 mmol). The flask was capped and stirred at room temperature for 1 h. Purification of the crude material was performed by injecting the solution directly onto a reverse phase HPLC (10-40% acetonitrile w/0.1% TFA/water w/0.1% TFA). The desired fractions were combined and concentrated in vacuo. The recovered material was taken up in 1 mL dichloromethane and 1 mL acetonitrile. A 6 mL tube packed with PL-HCO3 (Stratospheres Solid Phase Extraction macroporous resin for Acid Removal, Varian Industries) was pretreated with 2 mL of dichloromethane. The product solution was added to the top of the resin via pipette and was allowed to freely pass through the column via gravity. The column was rinsed with dichloromethane (2 mL) and acetonitrile (2 mL). The recovered filtrate was concentrated in vacuo to afford the title compound (23 mg, 59%). MS(ES)+ m/e 472.2 [M+H]+.

後処理

  1. customInto a 50 mL round bottom flask was placed
  2. additionAdded
  3. concentrationwas concentrated in vacuo
  4. additionAdded to flask
  5. customThe flask was capped
  6. stirringstirred at room temperature for 1 h
  7. customPurification of the crude material
  8. concentrationconcentrated in vacuo
  9. customA 6 mL tube packed with PL-HCO3 (Stratospheres Solid Phase Extraction macroporous resin for Acid Removal, Varian Industries)
  10. additionThe product solution was added to the top of the resin via pipette
  11. washThe column was rinsed with dichloromethane (2 mL) and acetonitrile (2 mL)
  12. concentrationThe recovered filtrate was concentrated in vacuo

出典と根拠

ORDレコード
ord-91a094ba0cb44afaae6b35232fb9c0ef
出典データセット
uspto-grants-2016_05
特許番号
US09340529B2

反応ノート

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