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

HRID 560021Notes

Reaction equation

HRID 560021 reaction equation
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]

Participants

9

Reactant 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

Product 1

HCID 597331381-[2-(2-Fluoro-6-methoxy-phenoxy)-4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-3-thiazol-2-yl-ureaYield 667.8%

Reagents, catalysts & solvents 2

HCID 5943Carbon TetrachlorideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-3756dfcf6fb24a619695f5f4b6118fd0
Source dataset
uspto-grants-2011_11
Patent number
US08063081B2

Reaction notes

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