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2-Aminothiazole → 1-[2-(2-Fluoro-6-methoxy-phenoxy)-4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-thiazol-2-yl-urea

HRID 560021
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HRID 560021 반응식
FC1C=CC=C(OC)C=1OC1C([N+]([O-])=O)=C(C)C=CC=1.BrN1C(=O)CCC1=O.C(OO[C:39](=[O:46])C1C=CC=CC=1)(=O)C1C=CC=CC=1.CN1CCNCC1.[F:54][C:55]1[CH:76]=[CH:75][CH:74]=[C:73]([O:77][CH3:78])[C:56]=1[O:57][C:58]1[CH:64]=[C:63]([CH2:65][N:66]2[CH2:71][CH2:70][N:69]([CH3:72])[CH2:68][CH2:67]2)[CH:62]=[CH:61][C:59]=1[NH2:60].[NH2:79][C:80]1[S:81][CH:82]=[CH:83][N:84]=1>C(Cl)(Cl)(Cl)Cl.C1COCC1>[F:54][C:55]1[CH:76]=[CH:75][CH:74]=[C:73]([O:77][CH3:78])[C:56]=1[O:57][C:58]1[CH:64]=[C:63]([CH2:65][N:66]2[CH2:67][CH2:68][N:69]([CH3:72])[CH2:70][CH2:71]2)[CH:62]=[CH:61][C:59]=1[NH:60][C:39]([NH:79][C:80]1[S:81][CH:82]=[CH:83][N:84]=1)=[O:46]
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참가 물질

9

반응물 6

HCID 21552-AminothiazoleHCID 7187Benzoyl PeroxideHCID 531671-MethylpiperazineHCID 67184N-bromobutanimideHCID 669988652-(2-Fluoro-6-methoxy-phenoxy)-4-(4-methyl-piperazin-1-ylmethyl)-anilineHCID 669990333-(2-Fluoro-6-methoxyphenoxy)-nitrotoluene

생성물 1

HCID 59733138
1-[2-(2-Fluoro-6-methoxy-phenoxy)-4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-thiazol-2-yl-urea
수율 667.8%

시약·촉매·용매 2

HCID 5943Carbon Tetrachloride용매HCID 8028Tetrahydrofuran용매

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온도
60 °C

실험 절차

3-(2-fluoro-6-methoxyphenoxy)-nitrotoluene (0.28 g, 1.0 mmol) was heated with N-bromosuccinimide (200 mg, 1.1 mmol) and dibenzoyl peroxide (10 mg) in CCl4 (10 mL) at 90° C. for 3 hr. The reaction mixture was cooled, filtered and the filtrate was concentrated. To the residue was added N-methylpiperizine (110 mg, 1.1 mmol) in THF (5 mL) and the mixture was heated at 60° C. for 4 hr. The volatiles were removed under reduced pressure. The residue was dissolved in ethyl acetate and washed (brine), dried (Na2SO4) and concentrated. The resulting nitrobenzene was reduced to 2-(2-fluoro-6-methoxy-phenoxy)-4-(4-methyl-piperazin-1-ylmethyl)-aniline (224 mg, 65%) following the general procedure C. 1-[2-(2-Fluoro-6-methoxy-phenoxy)-4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-thiazol-2-yl-urea (130 mg, 55%) was prepared from 2-(2-fluoro-6-methoxy-phenoxy)-4-(4-methyl-piperazin-1-ylmethyl)-aniline (172 mg, 0.5 mmol) and 2-aminothiazole (60 mg, 0.6 mmol) following the general procedure D.

후처리

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered
  3. concentrationthe filtrate was concentrated
  4. customThe volatiles were removed under reduced pressure
  5. dissolutionThe residue was dissolved in ethyl acetate
  6. washwashed (brine)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-3756dfcf6fb24a619695f5f4b6118fd0
출처 데이터셋
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08063081B2

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