Hydrochloric Acid → 1-(3-((4-(Ethylsulfonyl)piperazin-1-yl)methyl)-2-fluorophenyl)-3-(2-methylpyridin-4-yl)urea

HRID 2093444노트

반응식

HRID 2093444 반응식
[F:1][C:2]1[C:21]([NH:22][C:23]([NH:25][C:26]2[CH:31]=[CH:30][N:29]=[C:28]([CH3:32])[CH:27]=2)=[O:24])=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[CH2:10][CH2:9][N:8](C(OC(C)(C)C)=O)[CH2:7][CH2:6]1.Cl.CCN(CC)CC.[CH2:41]([S:43](Cl)(=[O:45])=[O:44])[CH3:42]>CO.C(Cl)Cl>[CH2:41]([S:43]([N:8]1[CH2:9][CH2:10][N:5]([CH2:4][C:3]2[C:2]([F:1])=[C:21]([NH:22][C:23]([NH:25][C:26]3[CH:31]=[CH:30][N:29]=[C:28]([CH3:32])[CH:27]=3)=[O:24])[CH:20]=[CH:19][CH:18]=2)[CH2:6][CH2:7]1)(=[O:45])=[O:44])[CH3:42]

참가 물질

7

반응물 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 11667Ethanesulfonyl chlorideHCID 58919226Tert-butyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)piperazine-1-carboxylate

생성물 1

HCID 236417451-(3-((4-(Ethylsulfonyl)piperazin-1-yl)methyl)-2-fluorophenyl)-3-(2-methylpyridin-4-yl)urea수율 90%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

실험 절차

To a solution of tert-butyl 4-(2-fluoro-3-(3-(2-methylpyridin-4-yl)ureido)benzyl)piperazine-1-carboxylate (600 mg, 1.35 mmol, 1.0 equiv) in MeOH (3 mL) was added HCl (4N in dioxane, 3 mL, 12 mmol, 8.9 equiv). After 1 h, the solvent was removed in vacuo. To this residue was added DCM (10 mL) and Et3N (875 μL, 6.28 mmol, 4.65 equiv), and the resulting solution was divided into two equal parts. To the resulting solution was added ethanesulfonyl chloride (90 μL, 0.95 mmol, 1.4 equiv) dropwise by syringe. After 30 min, the reaction was quenched by the addition of aq. satd. NaHCO3. The reaction was diluted with EtOAc, and washed twice with aq. satd. NaHCO3 and once with brine. The solution was then dried over sodium sulfate, filtered and concentrated in vacuo. Purification by reverse phase preparative HPLC provided 1-(3-((4-(ethylsulfonyl)piperazin-1-yl)methyl)-2-fluorophenyl)-3-(2-methylpyridin-4-yl)urea (267 mg, 90%). LCMS m/z (APCI)=436.2 (M+H).

후처리

  1. customthe solvent was removed in vacuo
  2. waitAfter 30 min
  3. customthe reaction was quenched by the addition of aq. satd
  4. additionThe reaction was diluted with EtOAc
  5. washwashed twice with aq. satd
  6. dry with materialThe solution was then dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by reverse phase preparative HPLC

출처 및 근거

ORD 기록
ord-c1d12b5ce8ec4a96adb9fc85d16804c2
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445495B2

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