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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
ノート
印刷プレビュー

反応式

HRID 2095897 の反応式
[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
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 6228
Dimethylformamide
触媒
HCID 65578Oxalyl chloride触媒
HCID 8028Tetrahydrofuran溶媒
HCID 31374Dimethylacetamide溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-add98eb8f5f64ee7afdbc359823ebbc7
出典データセット
uspto-grants-2013_05
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08445509B2

反応ノート

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