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 525254노트

반응식

HRID 525254 반응식
[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]

참가 물질

7

반응물 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

생성물 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-one수율 59.5%

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

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]+.

후처리

  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

출처 및 근거

ORD 기록
ord-91a094ba0cb44afaae6b35232fb9c0ef
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09340529B2

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