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Water → N-[4-({2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)-3-fluorophenyl]-N'-phenylcyclopropane-1,1-dicarboxamide

HRID 2095897
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HRID 2095897 반응식
[C:1]1([NH:7][C:8]([C:10]2([C:13]([OH:15])=O)[CH2:12][CH2:11]2)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[NH2:16][C:17]1[CH:38]=[CH:37][C:20]([O:21][C:22]2[CH:36]=[CH:35][C:25]3[N:26]=[C:27]([NH:29][C:30]([CH:32]4[CH2:34][CH2:33]4)=[O:31])[S:28][C:24]=3[CH:23]=2)=[C:19]([F:39])[CH:18]=1.O>O1CCCC1.CN(C)C=O.CN(C)C(=O)C.C(Cl)(=O)C(Cl)=O>[CH:32]1([C:30]([NH:29][C:27]2[S:28][C:24]3[CH:23]=[C:22]([O:21][C:20]4[CH:37]=[CH:38][C:17]([NH:16][C:13]([C:10]5([C:8]([NH:7][C:1]6[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=6)=[O:9])[CH2:11][CH2:12]5)=[O:15])=[CH:18][C:19]=4[F:39])[CH:36]=[CH:35][C:25]=3[N:26]=2)=[O:31])[CH2:33][CH2:34]1
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참가 물질

8

반응물 3

HCID 962WaterHCID 190968711-(Phenylcarbamoyl)cyclopropanecarboxylic acidHCID 58158640N-[6-(4-amino-2-fluorophenoxy)-1,3-benzothiazol-2-yl]cyclopropanecarboxamide

생성물 1

HCID 86651398N-[4-({2-[(cyclopropylcarbonyl)amino]-1,3-benzothiazol-6-yl}oxy)-3-fluorophenyl]-N'-phenylcyclopropane-1,1-dicarboxamide수율 57%

시약·촉매·용매 4

HCID 6228
Dimethylformamide
촉매
HCID 65578Oxalyl chloride촉매
HCID 8028Tetrahydrofuran용매
HCID 31374Dimethylacetamide용매

실험 절차

To a solution of 1-(phenylcarbamoyl)cyclopropanecarboxylic acid (214 mg, 1.04 mmol) in tetrahydrofuran (2 mL) were added oxalyl chloride (178 μL, 2.08 μmol) and N,N-dimethylformamide (2 drops) under ice-cooling, and the mixture was stirred at room temperature for 3 hr. The solvent was evaporated under reduced pressure. To a solution of the obtained residue in N,N-dimethylacetamide (5 mL) was added N-[6-(4-amino-2-fluorophenoxy)-1,3-benzothiazol-2-yl]cyclopropanecarboxamide (275 mg, 0.80 mmol), and the mixture was stirred at room temperature for 18 hr. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20→20/80, NH silica gel, hexane/ethyl acetate=50/50→0/100) and recrystallized from ethyl acetate to give the title compound (241 mg, 57%) as white crystals.

후처리

  1. temperaturecooling
  2. customThe solvent was evaporated under reduced pressure
  3. stirringthe mixture was stirred at room temperature for 18 hr
  4. extractionthe mixture was extracted with ethyl acetate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20→20/80, NH silica gel, hexane/ethyl acetate=50/50→0/100)
  7. customrecrystallized from ethyl acetate

출처 및 근거

ORD 기록
ord-add98eb8f5f64ee7afdbc359823ebbc7
출처 데이터셋
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08445509B2

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