Water → ethyl 4-[2-(4-fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl]-4H-pyridine-1-carboxylate

HRID 1803874노트

반응식

HRID 1803874 반응식
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]4)=[N:12][N:11]3[CH:23]=2)=[CH:4][CH:3]=1.Cl[C:25]([O:27][CH2:28][CH3:29])=[O:26].O.[N:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]4)=[N:12][N:11]3[C:23]=2[CH:34]2[CH:35]=[CH:36][N:31]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[CH:32]=[CH:33]2)=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 1049Pyridine2회HCID 10928Ethyl chloroformate3회HCID 594069602-(4-Fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazine

생성물 1

HCID 59406952ethyl 4-[2-(4-fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazin-3-yl]-4H-pyridine-1-carboxylate

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a suspension, cooled to about 0° C., of 3.24 g (10.4 mmol) of 2-(4-fluorophenyl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazine in 7.5 mL of pyridine is added dropwise a solution of 5.0 mL (52 mmol) of ethyl chloroformate. After cooling to room temperature, 10 mL (104 mmol) of ethyl chloroformate and 15 mL of pyridine are added in two portions. After 18 hours, the mixture is diluted with 50 mL of dichloromethane and 20 mL (208 mmol) of ethyl chloroformate are added in three portions over 5 hours. 350 mL of water are then added, and the organic phase is separated out and washed twice with water, dried over sodium sulfate and concentrated under reduced pressure to give 4.5 g of a brownish solid. This solid is triturated in diethyl ether to give 3.5 g of beige-colored crystals. The solid is dissolved in dichloromethane and purified by chromatography on a column of silica gel, eluting with a mixture of 10% methanol in dichloromethane, to give 2.95 g of pale yellow crystals after trituration in diethyl ether, filtering through a sinter funnel and drying under vacuum.

후처리

  1. additionare added in three portions over 5 hours
  2. customthe organic phase is separated out and
  3. washwashed twice with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-691e14969d92485ea8faf68c36d9c0cd
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08354405B2

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