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

HRID 2095897Notes

Reaction equation

HRID 2095897 reaction equation
[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

Participants

8

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 65578Oxalyl chlorideCatalystHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-add98eb8f5f64ee7afdbc359823ebbc7
Source dataset
uspto-grants-2013_05
Patent number
US08445509B2

Reaction notes

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